Neurology Firecracker

(1)

Ear Pathology

12 questions

339

The most common disorders of the ear are otitis

media, otosclerosis, labrynthitis, andcarcinoma of external ear.

Otitis media describes an inflammation of the middle ear, it is

mainly a pediatric illness.

less • Otitis media typically begins as a viral infection which then

is complicated by a bacterial super infection.

• The three most common species of bacteria implicated in otitis media are

• Streptococcus pneumoniae

• Haemophilus influenzae

• Moraxella catarrhalis.

• Chronic otitis media results from repeated acute

infections. Chronic infections often do not resolve completely.

• Cholesteatoma describes a cystic lesion of the middle ear

that may result in perforation of the tympanic membrane. It is often a complication of chronic otitis media.

Labyrinthitis describes an acute inflammation of the inner ear. It

often occurs immediately after an upper respiratory tract infection.

less • Symptoms of labyrinthitis include:

• tinnitus, vertigo

• hearing loss

• loss of balance

(2)

Treatment is usually conservative and symptomatic as the condition generally resolves on its own.

Otosclerosis describes a fusion of the ossicles in the middle

ear. It is a common form of conductive hearing loss in adults. Carcinoma of the external ear describes a malignant epithelial tumor which occurs most commonly on the pinna. It is often squamous cell carcinoma or a basal cell carcinoma and is linked to ultraviolet radiation.

less • Squamous cell carcinoma presents as a nodular, ulcerated

lesion.

• Basal cell carcinoma may present as telangiectatic, pearly papules.

Disorders of Special Senses

339

Deafness describes a loss of hearing. This can be further

classified as either conductive deafness or sensorineural

deafness, a differential which can be determined using specific

auditory tests. See auditory

system https://med.firecracker.me/topics/3442

less • Conductive deafness describes a deficit in the mechanical

conduction of sound. It is often a consequence of outer and middle ear pathology (seehttps://med.firecracker.me/topics/149).

• Otosclerosis describes a fusion of the middle ear ossicles.

It is the most common cause of conductive deafness in the elderly.

(3)

• Otitis media describes an infection of them middle ear. It is

the most common cause of conductive deafness in children.

• Sensorineural deafness describes a deficit in the neural

perception and transmission of sound. It is often a consequence of inner ear pathology.

• Presbycusis describes a degeneration of cochlear hairs. It

is the most common cause of sensorineural deafness in the elderly.

• Additionally, sensorineural deafness may result from compression of thevestibulocochlear nerve (Cranial

Nerve VIII) at the cerebellopontine angle. This is often a

consequence of mass effects of tumors such as Acoustic

Neuromas (Schwannomas) and less commonly meningiomas. • Therapeutic options for sensorineural deafness include

cochlear implants and hearing aids.

Anosmia describes a loss of the sense of smell, it may occur as

a result of damage to any structure of the olfactory pathway.

less • The olfactory tract is particularly vulnerable to traumatic

(skull fractures) or infectious (meningitis) damage or mass

effects from tumors such as meningiomas. These deficits tend to be ipsilateral.

• Meningiomas arising in the anterior fossa can result

in Kennedy Foster syndrome, which presents with clinical triad of ipsilateral anosmia, ipsilateral optic atrophy, and contralateral papilledema.

• Failure of the olfactory bulb to develop results in Kallmann

Syndrome, which presents with both bilateral anosmia as well

as hypogonadism, the latter being a consequence of the fact that Gonadotropin Releasing Hormone (GnRH) secreting neurons initially arise in the olfactory bulb before migrating to the medial preoptic nucleus of the hypothalamus.

• Lesions or seizures involving the parahippocampal

(4)

of the olfactory pathway with the limbic system. Special Senses https://med.firecracker.me/topics/2935

Ageusia describes a loss of taste. The most common cause is

heavy smoking.

less • Ageusia may also result from damage to any of the neural

structures involved in the gustatory pathway, including cranial nerves VII, IX, and X.

Blindness describes a loss of vision. It may be a result of either

eye pathology (https://med.firecracker.me/topics/934) or lesions of the optic pathway (https://med.firecracker.me/topics/3434).

less • Night blindness may be a consequence of Vitamin A

deficiency.

Cerebrovascular Hemorrhages

339

Intracerebral hemorrhage: bleeding into brain parenchyma

less • Intracerebral hemorrhage can result from:

- Hypertension (acute hypertension=most common cause) - Tumor encroachment on vessels

- Cerebral amyloid angiopathy

• Chronic hypertension → small vessel vasculopathy →

predisposes to the formation of Charcot-Bouchard aneurysms, which may rupture due to the increased wall stress caused by hypertension → intracerebral hemorrhage

Note:

Charcot-Bouchard aneurysms = microaneurysms that occur in the small perforating arteries of the brain—for example:

(5)

- Lenticulostriate vessels (most common site) - Thalamoperforator vessels

- Paramedian branches of the basilar artery - Superior cerebellar arteries

- Anterior inferior cerebellar arteries

• Most common sites of hypertensive bleeds in the CNS (in descending order of frequency):

1) Basal ganglia is most common site—50-60% of these basal ganglia bleeds originate in the putamen. Mechanism →

Lenticulostriate vessels (branches of MCA) are susceptible to high pressure damage.

2) Thalamus 3) Pons

4) Cerebellum

• Cerebral amyloid angiopathy involves the same amyloid protein found in Alzheimers disease:

- Deposition of -amyloid protein in cortical vessels β →

weakening of vessel walls → ↑ risk for lobar (eg, frontal, temporal, parietal, occipital cortex) intracerebral hemorrhage - Primary etiology of lobar hemorrhage is usually cerebral amyloid angiopathy, nothypertension

Subarachnoid hemorrhage: bleeding into subarachnoid space

less • Xanthochromia (blonde color) of the CSF after a

subarachnoid hemorrhage is caused by oxyhemoglobin and bilirubin

• Frequently caused by berry aneurysm (also known as a “saccular” aneurysm) of the circle of Willis (patients complain of a sudden worst headache)

(6)

Much more common in the anterior segment of the circle of Willis

Highly predictable spatial distribution:

- 40% at junction of anterior communicating artery and anterior cerebral artery

- 34% at bifurcation of MCA

- 20% at junction of ICA and posterior communicating artery - 4% at bifurcation of basilar artery

Commonly seen in:

- Coarctation of the aorta - polycystic kidney disease - Marfan syndrome

- Ehlers-Danlos syndrome

• Can be associated with arteriovenous malformations or trauma

• Potential complication: vasospasm. May be prevented by calcium channel blockers.

(7)

The presence of intracellular components of RBCs → ↑ potential for vasospasm.

General note:

Any increase in intracranial pressure is initially compensated by shifting of cerebrospinal fluid into spinal subarachnoid space

Viral infections

339

Can be limited to meninges (meningitis), involve entire brain (encephalitis), or both (meningoencephalitis)

Viral meningitis CSF profile: lymphocytes, moderate protein, ↑ ↑

normal glucose

Examples of viral infection:

Arbovirus encephalitides (St. Louis, eastern equine, western equine): mosquito vector

HSV (herpes simplex virus) encephalitis: seen in teenagers

and young adults, localized to temporal region.

Rabies:

- Can be aborted by active immunization before the onset of clinical manifestations

- Characterized by formation of Negri bodies, which are

eosinophilic intracytoplasmic inclusions commonly found in the hippocampus and Purkinje cells of cerebellum.

CMV (cytomegalovirus) encephalitis:

- Common in immunosuppressed patients

- Characterized by large intranuclear basophilic inclusions (surrounded by a clear halo, (offset)) and smaller

(8)

- Encephalomyelitis accompanied by kidney, liver, and/or lung lesions. In infants, periventricular calcifications with

chorioretinitis, hepatosplenomegaly, and mental retardation are common.

HIV encephalitis: characterized by diffuse myelin damage

(spongy myelinopathy with gliosis), neuronal loss, vascular damage, lymphocytic infiltrates in white matter, and

multinucleated giant cells (formed from fusing of membranes of infected macrophages).

less • May manifest as AIDS dementia complex: personality

changes, depression, difficulty with balance

Poliomyelitis: degeneration and necrosis of anterior horn cells of spinal cord

Slow progression viral infections: two types of viral CNS infection that have a slow clinical progression

less • 1) Subacute sclerosing panencephalitis

• Persistent infection with an altered measles virus

• Infected during infancy but will not manifest with

neurological symptoms until early teenage years, usually fatal

• Characteristic: CSF contains oligoclonal immunoglobulins against viral proteins

• 2) Progressive multifocal leukoencephalopathy

• Caused by JC polyoma type of papovavirus, which infects oligodendrocytes (inclusion bodies may be seen on microscopy) and astrocytes.

• Damaged oligodendrocytes → multifocal demyelination in brain

• Associated with leukemia, lymphoma, or HIV

Acute disseminated encephalomyelitis

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An acute inflammatory and demyelinating disease, ADEM is characterized by multiple foci of demyelination throughout the brain and spinal cord.

less • Usually follows a viral illness, such as measles, mumps,

rubella, varicella zoster, Epstein Barr, herpes simplex or coxsackievirus (also known as postinfectious encephalitis)

• Rarely, ADEM may occur after vaccination or bacterial infection. (Though it can occur at any age, most cases are in children and adolescents.)

Delayed hypersensitivity reaction. Symptoms include fever, headache, seizures and coma. These symptoms begin 1-3

weeks after infection or vaccination and may worsen rapidly. Full recovery is seen in most cases, but several patients may recover with minor residual disability. Average time to recovery is 1-6 months.

Widespread demyelination, particularly in subcortical and central white matter. Treatment involves high dose intravenous

corticosteroids and immunoglobulin.

Alzheimer disease

339

Alzheimer disease (AD): most common type of

dementia (about 60% of all dementias), incidence increases with

age

(10)

• Clinical course : insidious onset with progressive deterioration

characterized by gradual loss of memory and intellectual abilities with one (or more) of the following cognitive disturbances:

1. Aphasia (impaired language abilities)

2. Apraxia (impaired ability to execute voluntary motor activities despite intact ability to comprehend the task and intact

sensorimotor function)

3. Agnosia (impaired ability to recognize or identify objects despite

intact sensory function)

4. Disturbance in executive function (e.g. planning, organizing)

• Psychiatric manifestations are also common: personality changes, aggressive behavior, depression, sleep disturbances, paranoid thoughts and delusions

• In the late stages patients are often severely demented (sometimes even psychotic) with devastating memory loss →

bedridden → eventual coma and death

(commonly within 8-10 years of clinical diagnosis)

Many factors are associated with increased frequency of AD, including age, female sex, history of head trauma, Down syndrome, and genetics

less • Early-onset AD mutations: amyloid precursor protein β

(A PP) gene on chromosome 21, presenilin-1 gene on β

chromosome 14, or presenilin-2 gene on chromosome 1 (presenillin part of a complex for gamma-secretase enzymes involved in degrading amyloid beta proteins)

• Down syndrome patients almost universally develop AD by 40 years of age (extra chromosome 21 → increased expression of A PP gene)β

(11)

• A PP mutations β → abnormal A production with β

aggregation in neurons → metabolizing enzymes like alpha-secretase unable to degrade proteins → neuritic “senile” plaques

• Gene for ApoE4 (on chromosome 19) shown to have an association with AD, while the gene for ApoE2 (also on

chromsome 19) shown to have protective effect

Major pathologic features of AD are cerebral and hippocampal atrophy with characteristic histological changes of neurofibrillary tangles and senile plaques

less • NFTs (neurofibrillary tangles):

- Intracytoplasmic, basophilic inclusions which encircle or displace the nucleus of the host neuron

- Composed predominantly of paired helical

filaments containing abnormally hyperphosphorylated forms

of tau protein.

- NFTs are also found in other diseases (e.g., Pick disease) ∴ NFTs are not specific for Alzheimer disease!

Note: tau is an axonal microtubule-associated protein that

normally facilitates microtubule assembly; tau becomes insoluble

• “Senile” plaques : extracellular amyloid core that may β

cause amyloid angiopathy

• Amyloid angiopathy: amyloid deposition around vessels

leading to lobar intracranial hemorrhage

• Granulovacuolar degeneration: atrophy of hippocampus

consisting of small vacuoles within cell body, each vacuole having small dense inclusion

• Hirano bodies: intracytoplasmic proximal dendritic

eosinophilic inclusions of actin

• Degeneration of cholinergic cells that project to the cortex from the basal forebrain, especially the nucleus basalis of

Meynert (main approach to enhancing cognition is to give acetylcholinesterase inhibitors to increase cholinergic function)

(12)

Most effective initial interventions involve providing structured

environment, specifically visual-orienting clues (labels over

doors of rooms identifying their function, daily written activity of schedules, and practical safety measures like disconnecting the oven)

Medications: Acetylcholinesterase inhibitors (tacrine, donepezil, rivastigmine, and galantamine) and

an NMDA antagonist (memantine) to slow progression of the disease

For treatment and prognosis, important to make distinction between Alzheimer disease, pseudodementia and normal aging

less • Alzheimer disease: insidious onset, severe memory loss,

cognitive problems, decrease in IQ, disruption of normal life

• Pseudodementia, a depression that mimics dementia: abrupt onset, moderate memory loss, cognitive problems, no decrease in IQ, previous psychiatric history (antidepressants or psychotherapy can help)

• Normal aging: minor forgetfullness, reduced ability to learn new things quickly, no decrease in IQ, no disruption of normal life (no intervention needed except practical and emotional support from physician)

her causes of Dementia

339

Vascular dementia: second most common type of dementia,

caused by cerebral atherosclerosis and vascular insult.

(13)

• Three major mechanisms of vascular insult: multiple cortical infarcts, single and strategic infarct, and small vessel disease.

• Binswanger’s disease is a form of dementia caused by

diffuse subcortical infarcts, usually resulting from chronic

hypertension.

• Multi-infarct dementia: multiple, severe infarcts, causing a step-wise decline in cognitive function. Emphasis in treatment is on prevention of additional infarcts (anticoagulants like

coumadin or aspirin).

Infectious diseases: common in immunocompromised patients and the elderly.

less • Chronic infections: cryptococcus, neurosyphilis, and Lyme

disease.

• HIV-associated neurocognitive disorder (HAND): improves with antiretroviral therapy. HIVassociated disorders, such as progressive multifocal leukoencephalopathy (PML), can also cause dementia.

• Prion diseases such a Creutzfeldt-Jakob: rapidly progressive dementia, culminating in death.

Alcoholism: the etiology of dementia secondary to chronic

alcoholism is multifactorial. However, of the possible etiologies, the most important is Wernicke dementia due to thiamine

(vitamin B1) deficiency.

less • Wernicke dementia (sometimes called Wernicke

encephalopathy or Wernicke-Korsakoff syndrome): Triad—“Eyes, lies capsize”

1. “Eyes”—ophthalmoplegia (e.g., nystagmus) 2. “Lies”—confusion with confabulation

(14)

Severe atrophy of the brain—the most severe atrophy characteristically occurs in themammillary bodies.

• Tx for Wernicke syndrome: administer thiamine. Untreated, may result in rapid decline to death.

• Korsakoff psychosis, which is associated with alcoholism and Wernicke syndrome, is an irreversible chronic encephalopathy with antegrade and retrograde amnesia and confabulation.

Nutritional deficiencies: thiamine (vitamin B1), niacin (vitamin B3), or cobalamin (vitamin B12). Improves with vitamin

supplementation.

Heavy metal toxicity: cognitive impairment, often with

peripheral neuropathy. Often occurs in old homes or industrial

jobs. Tx: Chelation therapy specific for heavy metal.

less • Lead and copper (Wilson’s disease) are most common.

The only non-toxic heavy metal is gold.

Traumatic brain injury can cause dementia. Dementia

pugilistica is a form of delayed, head-trauma related dementia, seen mainly in boxers.

less • Can take decades for damage to become evident.

Frontotemporal lobar degeneration (Pick disease): presents

with alterations in personality, social behavior, and/or language progressive deterioration of these faculties with eventual

→

progression to global dementia.

less • Pronounced atrophy of the frontal and temporal lobes

with sparing of the posterior 2/3rds of the superior temporal gyrus:

1. Frontal lobe degeneration → personality changes, abulia, and disinhibition.

2. Temporal lobe degeneration → impaired understanding of language.

• NFTs (neurofibrillary tangles): Alzheimer disease vs. Pick

(15)

In both Alzheimer disease and Pick disease, NFTs begin as intracytoplasmic, basophilicinclusions which:

1. encircle or displace the nucleus of the host neuron 2. are composed predominantly of paired helical filaments containing aggregates ofabnormally

hyperphosphorylated forms of tau protein. (Normally, tau is

an axonal microtubule-associated protein that binds microtubules and facilitates their assembly; when damaged or distorted due to mutation or hyperphosphorylation, tau loses its ability to bind microtubules and instead tends to bind itself, forming

aggregates).

The NFTs in Alzheimer disease survive as "ghost"• or

"tombstone"• tangles long after the demise of the host neuron ∴ NFTs can be used as markers of disease severity. Indeed, in Alzheimer patients the number of NFTs correlates with the degree of dementia.

The NFTs in Pick disease are called Pick bodies. Unlike the NFTs of Alzheimer disease, Pick bodies do not survive the death of their host neuron ∴ cannot serve as a marker indicating the presence or severity of Pick disease.

DLB (dementia with Lewy bodies) — distinctive clinical

features (in addition to dementia) include: 1. Fluctuating cognition

2. Visual hallucinations—recurrent and often quite detailed

3. Parkinsonism—“pill-rolling” tremor; rigidity (cogwheeling may be present); bradykinesia; stooped, unstable posture; festinating gait; mask-like facies (i.e., decreased range of facial expression)

less • DLB is associated with Alzheimer’s disease; DLB patients

often have symptoms of both diseases.

(16)

In both Parkinson disease and DLB, Lewy bodies are intracytoplasmic, eosinophilic inclusions with a dense core (predominantly -synuclein) surrounded by a pale halo.α

In Parkinson disease, Lewy bodies can only be found in a narrow range of locations including the substantia nigra, locus ceruleus, dorsal motor nucleus of the vagus, and the basal nucleus of Meynert. In other words, Lewy bodies do not typically occur in cerebral cortical locations in patients with Parkinson disease. On the other hand, Lewy bodies in patients with DLB can be

found in a wide range of locations throughout the cerebral cortex in addition to the locations where they are

characteristically found in Parkinson disease (e.g.,

substantia nigra, locus ceruleus, dorsal motor nucleus of the vagus, basal nucleus of Meynert)

Huntington disease

339

Huntington disease: neurodegenerative trinucleotide expansion disorder that exhibitsanticipation — with each subsequent generation affected, age of onset and disease severity ↓ ↑

less • Huntington disease typically presents at age 30-40 → over

the next 15-20 years, patients experience progressive clinical decline characterized by choreiform and athetoid movements, mental disturbances (e.g., depression, psychosis), and

(17)

• Characteristics: “AC/DC”

Autosomal dominant

Choreiform (“dance-like”) movements

Dementia, Depression, and other mental Disturbance (e.g.,

psychosis)

Caudate atrophy is prominent on imaging and postmortem exam;

atrophy of the putamen and frontal cortex also occurs but is less prominent than caudate atrophy.

• Additional clinical features : - Hypertonicity

- Fecal/urine incontinence - Anorexia

- Athetoid movements (hallmark of basal ganglia insult) = slow writhing hand movements

• Especially depletes cholinergic and GABA-ergic neurons: - ↑ Dopamine

- ↓↓ GABA - ↓↓ ACh

• Atrophy of striatum (caudate nucleus and putamen) and frontal cortex.

Because the caudate nucleus borders the lateral ventral ventricles, atrophy of the caudate nucleus can lead

to hydrocephalus ex vacuo (i.e., the loss of brain matter bordering the ventricles makes the ventricles larger).

Caused by a (CAG)n trinucleotide expansion in

the Huntington gene located onchromosome 4 → “Hunt 4 an

animal and put it in a CAGe” (Caudate loses ACh andGABA)

less • No other novel mutations are known to cause the disease

• 1/12,000 → 1/20,000 = incidence in high-prevalence areas Transcription of BDNF gene (neuronal pro-survival factor) is decreased

(18)

Treatment:

- Reserpine + tetrabenazine: excess dopamine ↓ → ↓ dyskinesia - Haloperidol: dopamine receptor antagonist → ↓ dyskinesia

Brain Tumors

339

About one half to two-thirds of brain tumors are primary (from brain tissue) and the rest are metastatic.

Glioblastoma Multiforme (grade 4 astrocytoma):

Are GFAP positive

less • Most common primary intracranial CNS neoplasm in

adults; very poor prognosis (highly aggressive, rapidly-growing) • Located within white matter of cerebral hemispheres (often

in the centrum semiovale)—can spread to the contralateral hemisphere via the corpus callosum, straddling the cerebral hemispheres to form the classic “butterfly glioma”

• Histopathology:

1. Marked anaplasia (nuclear atypia, pleomorphism) with florid

vascular endothelial hyperplasia secondary to ↑ VEGF

2. Pseudopalisading necrosis—areas of necrosis and hemorrhage surrounded by rows of malignant cells

• CT with contrast or MRI with contrast: butterfly-shaped space-occupying lesion with central necrosis outlined by serpiginous, hetergenous contrast enhancement

Meningioma:

less • Most common benign intracranial neoplasm; 2nd most

(19)

• Meningiomas are benign slow-growing tumors that arise from meningothelial cells (most commonly the arachnoid mater) and are commonly located parasagitally (near the falx cerebri) or near the convexities of cerebral hemispheres.

• Although asymptomatic for years, meningiomas eventually become large enough to compress subjacent brain parenchyma

patients usually present with seizures

→

• Histology: whorled pattern of spindle cells with

psammoma bodies (laminated calcifications) Medulloblastoma:

less • 75% are found in children (median age 9).

Medulloblastoma accounts for 15-20% of all pediatric brain tumors

Indeed, medulloblastomas are the most common malignant

intracranial tumor in children.

• Most frequently arise in the posterior fossa (often in the cerebellum), where they may compress the 4th ventricle and impede CSF outflow via the midline foramen of Magendie and lateral foraminae of Luschka → hydrocephalus

• Histology: Hypercellular sheets of anaplastic cells.

• Medulloblastomas = PNET (primitive neuroectodermal

tumor) ∴ highly malignant. However, despite being incredibly

malignant, medulloblastomas are also radiosensitive.

Neuroblastoma:

less • Occurs almost exclusively in children

• Primary CNS neuroblastomas are very rare and usually cerebral.

• Neuroblastomas are most often found in adrenal medulla but can be found anywhere along the sympathetic chain

(20)

• Associated with N-myc oncogene amplification. ↑

Amplification → poor prognosis.

• Systemic metastases, especially to bone, have been observed

Retinoblastoma:

less • Most common primary ocular malignancy of childhood

(generally found in children under age 6)

• Retina location, unilateral or bilateral

• Commonly discovered on fundoscopic exam, which

reveals leukocoria: instead of seeing a red reflex, the examiner will see a white mass.

• Linked to homozygous deletion or inactivation of Rb

gene (chromosome 13) Schwannoma:

less • Acoustic schwannoma: third most common primary

intracranial neoplasm. Usually unilateral.

• Typically presents in middle-aged patients with progressive sensorineural hearing loss, tinnitus

• Occur on the vestibular division of CN VIII at the cerebellopontine angle

Encapsulated tumor arising from Schwann cells

• Histology: Nuclei arranged in “palisades”

• Benign and resectable

• Bilateral acoustic neuromas (benign schwannomas usually occurring on the vestibular division of CN VIII) are diagnostic of neurofibromatosis type 2

Oligodendroglioma:

less • Typically affects middle-aged pts

(21)

• Histology: closely packed cells with large nuclei

surrounded by clear halo of cytoplasm—“fried egg” appearance

• Slow growing and rare

Astrocytoma (pilocytic): Are GFAP positive

less • Affects young children.

Low grade gliomas (including pilocytic astrocytomas) are the most common type of brain tumor in children.

• Posterior fossa location and circumscribed

• Histology: Rosenthal fibers—eosinophilic corkscrew

fibers

• Benign, low grade, good prognosis

Ependymomas are rare tumors of the ependymal cells, which

line the ventricular system of the brain and the central canal of the spinal cord.

less • Ependymomas are more common in children than in adults.

• In children, ependymomas tend to occur in the fourth ventricle and cause hydrocephalus. In adults, ependymomas occur most often in the spinal cord and may cause

syringomyelia.

Craniopharyngiomas are rare tumors derived from Rathke’s

pouch, the embryonic precursor of the anterior pituitary.

less • They are usually suprasellar in location and may compress

the optic chiasm, causingbitemporal hemianopsia.

• These tumors occur most often in children, and on exams are often presented as a child with a visual field defect.

Seizures

339

Seizures may be partial (affects one area of the brain) or generalized (diffuse)

However, partial seizures may progress to be generalized Epilepsy: used to describe condition of recurrent seizures

Causes for epilepsy: genetic, infection, trauma, stroke, metabolic (hypo or hypernatremia)

Simple partial seizures

less • Patient remains conscious

• Can manifest as motor, sensory, psychic, or autonomic changes

• Treatment: all anti-seizure drugs work effectively

Complex partial seizures

less • Patient has impaired consciousness

• Treatment: all anti-seizure drugs work effectively

Absence (Petit Mal) seizures

less • Usually in children, manifest as a blank stare

• Treatment: First line anti-seizures drug treatment is ethosuximide. Valproic acid is used as a second line agent

Myoclonic seizures

less • Repetitive jerks of the body or extremities

• Treatment: First line agent is valproic acid.

Tonic-Clonic (Grand Mal) seizures

less • Patient is tonic (stiff) and then becomes clonic (jerking

movements)

• The 3 first line anti-epileptics for tonic-clonic seizures have a similar mechanism ( Na channel inactivation) and can be ↑

remembered by “PVC”:

1. P henytoin (also first line for prophylaxis of status

(23)

2. V alproic acid (also used for myoclonic seizures)

3. C arbamazepine (also first line for trigeminal neuralgia)

Status epilepticus

less • Life threatening, persistent seizure activity in the brain

• Treatment: First line anti-seizure drugs are

benzodiazepines, such as diazepam. First line drug for prophylaxis is phenytoin to increase seizure threshold

Headaches

339

Migraines are POUNDing:

Pounding (pulsatile), phonophobia, photophobia One-day duration

Unilateral

Nausea or vomiting

Disabling due to excruciating pain (ie, so painful that it limits

routine activities) Compare to:

- Cluster headaches, which are also unilateral and disabling, but tend to be brief and are accompanied by autonomic Sx (eg, lacrimation, rhinorrhea, sweating, miosis, ptosis)

- Tension headaches, which are different from migraines in almost every respect: nonpulsating, bilateral, not disabling, not associated with nausea / vomiting

(24)

• Migraines can be accompanied by "aura": constellation of neurological symptoms which can affect the auditory, visual or olfactory system.

• Treatment:

- Migraines can be treated acutely with sumatriptan

- -blockers, TCAs or gabapentin are sometimes useful in β

migraine prophylaxis

Tension headaches:

less • Most common type of recurring headache.

• Generally associated with either muscular or psychological stressors.

• Key clinical features :

1. Bilateral, non-pulsating headaches often described by patients as a “band-like” pressing / tightening / squeezing pain around the head.

2. Only mildly or moderately painful ∴ not disabling 3. Not associated with nausea or vomiting

4. Not aggravated by routine movement (eg, climbing stairs)

• Generally responds well to NSAIDs

Cluster headaches:

less • Unilateral, brief headaches characterized by periorbital /

temporal pain as well asipsilateral autonomic symptoms in

the face (eg, lacrimation, rhinorrhea, sweating, miosis, ptosis)

• Occur in clusters — cluster headaches occur repeatedly within a “cluster” period of 3-6 weeks followed by month- or year-long periods without cluster headaches.

• High flow O2 or sumatriptan can be used to arrest an acute

episode.

Key comparisons — Migraine vs. Tension vs. Cluster headaches:

(25)

• Unilateral :

- Migraine headaches - Cluster headaches Bilateral:

- Tension headaches

• Excruciatingly painful ∴ disabling : - Migraine headaches

- Cluster headaches

Mildly / moderately painful not disabling∴ : - Tension headaches

Sinus headaches:

less • Worse when lying down

• Associated with nasal congestion, sinus tenderness, and maxillary tooth pain

Headache due to intracranial mass:

less • Worse in morning on awakening

• May be aggravated by : 1. Exercise

2. Sexual activity 3. Changing position

4. Valsalva maneuvers (expiring forcefully against a closed glottis) such as coughing, sneezing, straining on the toilet

• Associated with abnormal neurologic exam

Red-Flag signs of underlying pathology → require further work up

less • Sudden onset of severe persistent headache is suspicious

of SAH (subarachnoid hemorrhage) from ruptured berry aneurysm.

• Headache associated with Valsalva maneuver, exercise or sexual activity may indicate increased ICP (i.e. from space

(26)

• Headaches that awaken patients from sleep in the middle of the night.

• Fever accompanied by altered mental status suggests intracranial infection.

• Headache associated with neck stiffness or meningeal signs suggests meningitis or blood in the subarachnoid space.

• New onset headache in a patient < 5 years old or > 50 years old.

• New onset headache in a patient with a history of cancer.

Eye Pathology

339

Cataracts describe painless, bilateral opacities of the lens of the

eyes leading to a decrease in vision. They are the leading cause of blindness and have multiple etiologies.

less • Advanced age is the most common cause of cataracts.

Lens proteins denature and degrade over time, clouding the lens.

• Cataracts can form as a result of osmotic damage from sugar alcohol deposition within the lens. Such disease processes include uncontrolled diabetes mellitus via sorbitoldeposits

and classic galactosemia via galacticol deposits.

• Cataracts can be consequences of chromosomal

abnormalities such as trisomy 21 (Down syndrome), trisomy

18 (Edward’s syndrome), trisomy 13 (Patau syndrome),5p deletion (Cri-du-chat syndrome), and Turner’s syndrome.

(27)

• Congenital infections such as rubella, cytomegalovirus

(CMV), syphilis, and herpes simplex virus (HSV) can also

induce cataract formation.

• Other risk factors include elements which may lead to increased oxidative stress or physical trauma,

including cigarette smoking, steroid use, prolonged ultraviolet

(UV) radiation exposure, trauma, and alcohol consumption. Glaucoma describes an increase in intraocular pressure (IOP)

due to the disruption in the balance of aqueous humor production by the ciliary processes and drainage by the

trabecular meshwork, leading to optic nerve damage. It is the second most common cause of blindness.

less • Open (wide) angle glaucoma accounts for 90% of all

cases. It is characterized by an impaired outflow (e.g. Schlemm’s canal) of aqueous humor and an absence of symptoms, which may lead to a silent progression.

• Open angle glaucoma is most often idiopathic, but may also be due to mutations in the gene encoding the

protein myocilin.

• Risk factors for open angle glaucoma include advanced

age, African-American race,myopia, and diabetes mellitus. • Treatments for open angle glaucoma include

beta-blockers (Timolol), carbonic anhydrase inhibitors

(acetazolamide), and prostaglandin analogues (latanoprost). • Closed angle glaucoma is characterized by an occlusion

of flow between the iris and lens, resulting in rapid increase in IOP. It may be chronic or acute.

• Risk factors for closed angle glaucoma include Asian or

Inuit race, eye trauma, andintraocular infection.

• Acute closed angle glaucoma is an ophthalmologic

emergency that leads to irreversible vision loss within hours if left untreated.

(28)

• Symptoms of closed angle glaucoma include a red and very painful eye, blurry vision or seeing “halos”, a rock-hard eye, a dilated and non-reactive pupil, and a severe frontal headache with nausea and vomiting.

• Treatments for closed angle glaucoma include immediate laser or surgical iridotomy, in which a hole is made in the iris to reestablish the flow of aqueous humor, thereby relieving

intraocular pressure.

• Congenital glaucoma may be associated with a

developmental defect in the structure of the anterior chamber, as sometimes is seen in syndromes such as

Sturge-Weber,neurofibromatosis type I (NF1), or Marfan’s.

Age-related macular degeneration (ARMD) is characterized by

a loss of central vision due to age-related degeneration of the macula.

less • Nonexudative (“dry”) ARMD refers to an atrophy and

degeneration of central retinal pigment epithelial layer below the retina, which causes vision loss through loss of photoreceptors. It is characterized by an accumulation of an extracellular material known as drusen.

• Exudative (“wet”) ARMD results in a sudden visual loss

due to leakage of serous fluid into the retina as a result of abnormal vessel formation (neovascularization, hence “wet”) under retinal pigment epithelium. It is less common than dry ARMD.

• Risk factors for ARMD include:

• advanced age

• female gender

• Caucasian race

• smoking

• hypertension.

• Familial ARMD is associated with mutations

(29)

• Treatment options for wet ARMD include intraocular injections of anti-VEGF antibodies (ranibizumab and

bevacizumab) in order to decrease the rate of

neovascularization.

Retinal detachment describes a separation of the neurosensory

layer (part with rods and cones) of the retina from the pigment epithelium, leading to vision loss and blindness.

less • Symptoms of retinal detachment include brief, painless

flashes of light in the periphery and dense shadows that start

peripherally and moves centrally. Patients will claim a“curtain or

veil is blocking my vision”.

• Risk factors for retinal detachment include:

• myopia, as the retina in nearsighted people tends to be

more thinly stretched and thus prone to detachment

• proliferative retinopathy, as abnormal blood vessels

in the vitreous can pull the retina away from the back wall of the eye

• previous cataract surgeries

• diabetes

• trauma, as is sometimes seen in shaken baby

syndrome.

Hydrocephalus

339

Hydrocephalus is the pathological condition resulting from an

alteration of the normal flow of CSF, leading to compression of surrounding CNS tissue.

(30)

• The expansion of the CSF compartment often leads to the radiographic finding of enlarged ventricles.

There are 2 main classifications of hydrocephalus: communicating and non-communicating.

Communicating hydrocephalus: Caused

by decreased resorption of CSF by the arachnoid granulations. Unlike non-communicating, there is no blockage of CSF flow.

less • Arachnoid granulations can be damaged by meningitis or

subarachnoid hemorrhage.

The main type of communicating hydrocephalus is normal

pressure hydrocephalus(NPH), the symptoms of which can be

remembered with the mnemonic: “wacky, wobbly, wet.”

less • NPH is characterized by normal intracranial pressures. This

is because the increase inCSF takes place over time, thus allowing the gradual increases in ICP to be offset by

compression of the cerebral hemispheres.

• NPH presents with a clinical triad of dementia, gait

disturbances and bladder incontinence, hence wacky, wobbly,

wet.

• NPH should always be on the differential for a workup of dementia, because it’s one of the only treatable forms.

• Contrast NPH with an acutely occurring hydrocephalus caused from clogged arachnoid granulations after a

subarachnoid hemorrhage. In the latter case, there is no short-term cerebral compliance, thus life-threatening increases

in ICP can rapidly occur.

Non-communicating hydrocephalus takes place when there is a block at one of the narrow points in the CSF circulation.

less • The etiology is chiefly mass effect caused by edema,

tumors, or congenital abnormalities (Dandy-Walker and Chiari malformations).

• Babies with hydrocephalus develop macroencephaly

(31)

also develop the setting sun sign, where upward gaze palsy manifests as a predominant downward gaze.

Another clinical entity, hydrocephalus ex vacuo is somewhat of a misnomer. Since it is caused from brain atrophy and resulting widening of ventricles, it is more of a descriptive term, and not true hydrocephalus.

Neurologic Pain Syndromes

339

Trigeminal neuralgia (tic douloureux) causes brief but severe

attacks of unilateral facial pain limited to the distribution of divisions of the trigeminal nerve.

less • Often triggered by simple stimuli (brushing teeth, shaving

etc.).

• The cause is often unknown, but can be linked to an underlying disease process (MS, tumors, vascular disease).

• First-line treatment is with carbamazepine.

Complex regional pain syndrome, CRPS presents with intense regional pain following trauma, the pain being excessive

compared to the severity of trauma. Generally occurs in the extremities.

less • CRPS type I, also called reflex sympathetic dystrophy,

has no definable nerve lesion, whereas CRPS type II does.

• Both types are often associated with edema, decreased mobility, and autonomic dysfunction → changes in skin

temperature and color, sweating abnormalities.

• The pain is not limited to the area of the trauma, and frequently spreads to other areas.

(32)

• Patients with CRPS for over 2 months often require psychological assessment and treatment to help manage and cope with the symptoms.

Post-stroke pain can occur because of a lesion at any level of

the CNS, but most frequently occurs because of damage to the thalamus or brainstem.

less • In thalamic syndrome (Dejerine-Roussy syndrome)

following thalamic insult, there is initially contralateral body sensory loss followed by a period of intense pain that may last for years.

Emotional distress, loud noises, and cutaneous stimuli can worsen the pain.

• Treatment for post-stroke pain is difficult, and may include antidepressants, analgesics, and anticonvulsants.

Radicular pain is pain limited to the distribution of specific nerve

roots, and is often named according to the roots and nerves affected (e.g. sciatica).

less • Exacerbated by movements that stretch, compress, or

irritate the affected roots, or that increase intraspinal pressure.

Peripheral neuropathy can cause many symptoms including

pain.

Congenital Nervous System Disorders

339

Neural tube defects

(33)

• Associated with increased alpha fetoprotein in amniotic fluid

• Associated with maternal folic acid deficiency

Spina bifida – failure of posterior vertebral arches to close. Several forms which include:

less • 1) Meningocele – herniated membranes consisting of only

meninges

• 2) Meningomyelocele – herniated meninges and spinal cord

• 3) Spinal bifida occulta – vertebral arches do not form in lumbar area but spinal cord is normal. No symptoms, may have a lumbar dimple, lipoma, or tuft of hair on exam.

TORCHeS infections:

less • To xoplasma

Rubella CMV

Herpes simplex, HIV

Syphilis (Treponema pallidum)

• Associated symptoms include microcephaly, jaundice or hepatosplenomegaly.

Arnold-Chiari malformation

less • Arnold-Chiari Type I : Low lying cerebellar tonsils herniate

through the foramen magnum. Cervical syringomyelia (C8-T1) may also be present.

This can often be clinically silent.

• Arnold-Chiari Type II : Triad of - Small posterior fossa

(34)

- Misshapen midline cerebellum

- Downward extension of the cerebellar vermis through the foramen magnum.

• Results in obstruction of CSF (cerebrospinal fluid) outflow tract and causes hydrocephalus. May present with headaches, visual changes, seizures or confusion.

• Increased incidence of coexisting lumbosacral meningomyelocele.

Fetal alcohol syndrome: most common cause of mental

retardation (affecting 1 – 4.8 per 1000 children born in the US) — versus:

- Down syndrome: most common genetic cause of mental retardation

- Fragile X syndrome: most common inherited cause of mental retardation

less • Mental retardation due to CNS (central nervous system)

damage:

- prenatal alcohol exposure (especially during the first trimester) may disrupt crucial developmental pathways, including the

retinoic acid and Hedgehog pathways

• Growth retardation →

- small body size - microcephaly

- midface hypoplasia

• Midface abnormalities : 1) short palpebral fissures 2) epicanthal folds

3) long philtrum 4) thin upper lip

• Heart defects :

- VSD (ventricular septal defect) - ASD (atrial septal defect)

(35)

Trigeminal Neuralgia

339

Trigeminal neuralgia (tic douloureux) causes brief but severe

attacks of unilateral facial pain limited to the distribution of divisions of the trigeminal nerve.

less • Often triggered by simple stimuli (brushing teeth, shaving

etc.).

• The cause is often unknown, but can be linked to an underlying disease process (MS, tumors, vascular disease).

• Not associated with any motor or sensory paralysis

Dx: usually clinical. Can do an MRI to rule out cerebellopontoine

angle tumor

less • pts with cerebellopontoine angle tumor often have loss of

ipsilateral corneal reflex 2/2 mass effect from the tumor unlike patients with trigeminal neuralgia were no motor or sensory deficits are seen

Treatment:

• First line: Carbamazepine

• Second line: Baclofen or Phenytoin. Can be used in conjunction with Carbamazepine

• Surgical decompression if medical therapy fails

Epidural abscess

339

Life threatening infection that spreads in the epidural space and can compress the brain or the spinal cord leading to grave

permanent complications.

Risk Factors: IV drug abuse, HIV infection, bacteremia, surgical

procedures, epidural catheters (for pain control) Most common culprit: S Aureus

Presentation: classic triad of:

• Spinal pain

• Fever (sometimes) • Neural deficits DX: MRI > CT scan

less • Lumbar puncture should be done after imaging and lesion

localization, since passing a needle through the abscess could seed the subarachnoid space.

Treatment: Aspiration, drainage and antibiotics

• Early surgical intervention, within 24 hrs, is crucial especially if the abscess has already produced neural deficits 2/2 mass effect

• Antibiotics: Vancomycin + Metrondiazole (If pseudomonas

is a concern, add Ceftazidime)

• Drainage: can be achieved through burr holes or craniotomy

Brain abscess

(37)

Usually results from

• Trauma to the cranial space e.g. neurosurgery • ENT infection spread

• Dental infection Etiology:

• Strep – Sinusitis • S. Aureus – trauma

• Anaerobes – chronic otitis media

less • Most brain abscesses are bacterial, however, in

immunocompromised patients consider toxoplasmosis and fungal (Candida, Aspergillus) infections

Pt usually presents with neural focal deficits secondary to mass effect. Can be accompanied by headache, seizure activity, vomiting, nuchal rigidity.

less • Fever and chills are NOT always present

Dx: CT scan or MRI. Aspiration or surgical excision is both

therapeutic and diagnostic.

Tretament:

• IV Antibiotic: Pen G + Chloramphenicol or Metrondizaole • If MSSA is suspected → Nafcillin

• MRSA → Vancomycin

• Surgical drainage: diagnostic and therapeutic • Glucocorticoids: if mass effect is present

Amyotrophic lateral sclerosis

(38)

Etiology

less • Degeneration of upper AND lower motor neurons

• Sensory neurons are not damaged

• Atrophy of lateral corticospinal tracts

• Atrophy of anterior motor neurons of spinal cord.

• Results in denervation atrophy of muscles

• Two forms of ALS:

- Sporadic ALS (most common)

- Familial ALS (5-10% of cases): occurs more than once in a family. Hereditary defects in superoxide dismutase 1 (autosomal dominant) are associated with 20% of familialALS cases.

Clinical manifestations

less • Symmetric atrophy, fasciculation of muscles (lower motor

neuron signs)

• Symmetric hyperreflexia, spasticity and pathological reflexes (upper motor neuron signs)

• Results in rapid course, ending in respiratory failure. Treatment:

- Mostly supportive care (pain control, intubation by tracheostomy)

- Riluzole (blocks glutamatergic neurotransmission by inhibiting glutamate release and inactivating voltage-gated Na channels) is an FDA-approved medication that extends survival and/or time to tracheostomy, but only by a couple months.

Herniation Syndromes

(39)

Herniation syndromes occur when the brain expands and displaces the contents of the intracranial cavity.

Coma and death can result from compression of the brain stem by a herniation.

The brain and spinal cord are protected by the rigid

compartments comprised of the skull, vertebra, and dura mater.

Brain swells → vein compression and CSF displacement →

increased intracranial pressure → decreased perfusion of brain increasing swelling

→

Subfalcine (cingulated) herniation

less • Herniation occurs when a cerebral hemisphere displaces

the cingulated gyrus under the falx cerebri.

• Herniation may compress branches of the anterior cerebral artery. This may result in paralysis, weakness, and sensory loss of the contralateral foot and leg.

Transtentorial (uncinate, medial temporal) herniation

less • Herniation occurs when the medial aspect of the temporal

lobe compresses the free margin of the tentorium.

• Herniation may cause the following:

1) Compress CN III → pupillary dilation and impairment of ocular movements on the side of the lesion

2) Compress Posterior cerebral artery → hypoperfusion of the primary visual cortex

3) Compression of crus cerebri (cerebral peduncle) →

contralateral (to the crus cerebri) hemiparesis but ipsilateral to the lesion

(40)

• Note that pontine hemorrhages are also known as duret

hemorrhages.

Tonsilar herniation

less • Herniation occurs when the cerebellar tonsils are displaced

through the foramen magnum.

• Herniation is life-threatening because the brainstem compression affects respiratory and cardiac centers in the medulla oblongata.

• Tonsillar herniation can occur if an LP is performed on a patient with unrecognized hydrocephalus or a mass lesion leading to increased ICP.

LP should never be performed on a patient with ↑ ICP

Head injuries

339

Can result from penetrating wounds or nonpenetrating injuries (contusions)

In epidural hematomas, CT scan shows a highly attenuating convex ("lenticular") shaped mass overlying the brain. Epidural hematomas are also less likely to cross suture lines than

subdural hematomas.

less • Associated with skull fracture

• Arterial hemorrhage from laceration of middle meningeal artery (branch of the maxillary artery) near the temporal bone

• Characterized by lucid interval (brief period of

(41)

• Does not bleed into brain substance so amenable to emergent surgical evacuation to decrease intracranial pressure

Subdural hematoma:

less • Associated with venous bleeding from torn bridging veins

• More common in victims of abuse (e.g., shaken baby syndrome, elderly abuse) and in patients with atrophic brains prone to falls (e.g., alcoholics, elderly)

• Characterized by gradual signs of cerebral compression that may manifest in hours to days. In this scenario, an elderly person can have progressive confusion which goes unnoticed until a coma occurs.

• CT scan shows a crescent shaped (concave) hematoma which is less dense than an epidural hematoma due to dilution of the blood by CSF. Subdural hematomas are also more likely to cross suture lines than epidural hematomas.

Parkinson disease

339

Parkinson disease: idiopathic degenerative CNS disorder associated with:

1. Abnormal eosinophilic intracellular inclusions of -α synuclein known as Lewy bodies

2. Loss of dopaminergic neurons in the SNc (substantia

nigra pars compacta) → - dopamine↓

- ACh↑

(42)

• Mutations in the gene encoding the lysosomal enzyme

glucocerebrosidase (GBAgene on chromosome 1—GBA is the

same gene which is deficient in patients withGaucher disease!) risk of developing Parkinson disease

→ ↑

• Parkinson disease can sometimes be confused with progressive supranuclear palsy.

Progressive supranuclear palsy usually presents as an

isolated vertical gaze palsy, followed by paresis of other ocular movements, and signs and symptoms ofParkinsonism (ie, tremor, bradykinesia, rigidity, and postural instability).

Normally, dopamine is released from the nigrostriatal neurons (i.e., neurons originating in the SNc → terminating in the

striatum) to activate the direct pathway (D1 receptors) and inhibit

the indirect pathway (D2 receptors).

less • DIR ECT (excitatory) pathway :

Dopaminergic neurons in the SNc send excitatory output to striatal neurons with D1receptors (i.e., DA binds D1 receptors →

activation) → these striatal neurons send inhibitory (GABA) output to GPi/SNr → neurons in the GPi/SNr send inhibitory (GABA) output to VL nucleus of thalamus → neurons in VL nucleus of thalamus send excitatory (Glutamate) output to the motor cortex.

Normally:

Dopamine stimulates striatal neurons with D1 receptors → ↑

inhibition of GPi/SNr → disinhibition of thalamus → stimulation of motor cortex → ↑ in movement.

Parkinson disease:

Decreased striatal dopamine stimulation → ↓ inhibition of GPi/SNr → ↑ inhibition of thalamus → ↓ stimulation of motor cortex → in movement↓

(43)

• I NDIRECT ( i nhibitory) pathway :

Dopaminergic neurons in the SNc send inhibitory output to striatal neurons with D2receptors (i.e., DA binds D2 receptors →

inhibition) → these striatal neurons send inhibitory (GABA) output to GPe (globus pallidus externa) → neurons in the GPe send inhibitory (GABA) output to STN (subthalamic nucleus) →

neurons in the STN send excitatory (Glutamate) output to GPi/SNr → neurons in the GPi/SNr send inhibitory (GABA) output to VL nucleus of thalamus → neurons in VL nucleus of thalamus send excitatory (Glutamate) output to the motor cortex. Normally:

Dopamine inhibits striatal neurons with D2 receptors →

disinhibition of GPe → ↑ inhibition of STN → ↓ stimulation of GPi/SNr → ↓ inhibition of thalamus → stimulation of motor cortex

in movement.

→ ↑

Parkinson disease:

Decreased dopamine inhibition → ↑ inhibition of GPe →

disinhibition of STN → stimulation of GPi/SNr → ↑ inhibition of thalamus → → ↓ stimulation of motor cortex →↓ in movement

Classic presentation: use the mnemonic “TRAPpED”

- Tremor at rest (“pill-rolling” • tremor) → illegible handwriting - cogwheel Rigidity

- Akinesia

- Postural instability (stooped “simian” posture) with shuffling (“festinating”) gait

- Expressionless (mask-like) face

- risk of↑ Dementia (TRAPpED in your own body) Other Parkinson-like diseases:

less • Postencephalitic parkinsonism : viral etiology → influenza

(44)

• Trauma : especially in professional fighters with brain injury secondary to repetitive brain trauma sustained over years—e.g., Muhammad Ali, arguably the greatest professional boxer of all time, developed Parkinson disease after years of taking punches to the head.

• Drugs and toxins , especially dopamine

antagonists like MPTP

(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, a contaminant in the illegal street drug MPPP)

Treatment: use the mnemonic “BALSA”:

less • B romocriptine: dopamine receptor agonist (ergot alkaloid)

Note: Newer non-ergot dopamine receptor agonists such as

pramipexole and ropinirole are now preferred for the treatment of Parkinson disease over bromocriptine, which is associated with a less favorable side effect profile.

• A mantadine: dopamine secretion,↑ NMDA receptor inhibition

• L -DOPA/carbidopa: converted to dopamine in CNS → L-DOPA can cross blood-brain barrier; carbidopa is a peripheral decarboxylase inhibitor that increases the bioavailability of L-DOPA to the brain

• S elegiline + COMT inhibitor (e.g. entacapone or

tolcapone) : dopamine breakdown↓

• A ntimuscarinics like Benztropine can also be used to

treat Parkinson disease → ↓ tremor and rigidity (mnemonic: Park your Mercedes-Benz)

Tension Headache

339

Most common type of recurring headache.

Generally associated with either muscular or psychological stressors.

Key clinical features:

1. Bilateral, non-pulsating headaches often described by

patients as a “band-like” pressing / tightening / squeezing pain around the head.

2. Only mildly or moderately painful ∴ not disabling 3. Not associated with nausea or vomiting

4. Not aggravated by routine movement (eg, climbing stairs)

Generally responds well to NSAIDs

less • Excruciatingly painful ∴ disabling :

• Migraine headaches • Cluster headaches

Mildly / moderately painful not disabling∴ :

• Tension headaches

Cluster headache

339

(46)

• Unilateral :

Bilateral:

• Excruciatingly painful ∴ disabling :

Mildly / moderately painful not disabling∴ :

Unilateral, brief headaches characterized by periorbital /

temporal pain as well asipsilateral autonomic symptoms in

the face (eg, lacrimation, rhinorrhea, sweating, miosis, ptosis) Occur in clusters — cluster headaches occur repeatedly within a “cluster” period of 3-6 weeks followed by month- or year-long periods without cluster headaches.

High flow O2 or sumatriptan can be used to arrest an acute

episode.

Prophylaxis: Most responsive of all headaches to ppx.

• First line: Verapamil daily

• Second line: Ergotamine, Li, prednisone

Vertigo

(47)

Vertigo describes an illusion of rotary movement caused by an

acute asymmetry of neural impulses between left and right vestibular systems.

Peripheral vertigo encompasses all etiologies of vertigo which

involve the inner ear. It commonly presents with:

• tinnitus

• hearing loss

• prominent nausea and vomiting

less • Positional testing in peripheral vertigo reveals delayed

horizontal nystagmus, which is inhibited by fixation of eyes

onto object, and does not change direction with gaze to either side.

• The most common causes of peripheral vertigo are

• benign paroxysmal positional vertigo • acute vestibular neuritis

• Ménière’s disease

• Benign paroxysmal positional vertigo (BPPV) refers brief periods of vertigo which occur with change in position. It is due to freely moving crystals of calcium carbonate within

the semicircular canals.

• Ménière’s disease describes an intermittent increase in endolymphatic volume of the inner ear. This results in

episodic vertigo with nausea, vomiting, progressive hearing loss, and a sensation of fullness in the ear.

Central vertigo results from cerebellar or brainstem lesions and

is usually associated with cranial nerve signs (e.g. diplopia, dysarthria, dysphagia), weakness, ataxia, and other changes that may indicate a central process. Patients tend to suffer from a severe inability to stand still or walk.

less • Positional testing in central vertigo reveals immediate

(48)

not inhibited by fixation of eyes onto object, and can change direction with gaze towards the fast phase of the nystagmus.

Guillain-Barre syndrome

339

Acute inflammatory demyelinating disease which primarily

involves peripheral nerves, resulting in endoneurial inflammatory infiltrates

Highest incidence in young adults Autoimmune etiology

Associated with infections. Commonly present with muscle weakness preceded byCampylobacter jejuni infection.

less • In addition to C. jejuni, infections with an association

with GBS include H. influenzae, herpes viruses (CMV, EBV, VZV), and M. pneumoniae.

Clinical manifestation

less • Ascending muscle weakness and paralysis

• Begins in the lower part of extremities and ascends upwards

• Autonomic dysfunction, hypertension, orthostatic hypotension, EKG changes

• Most patients survive but severe cases can have respiratory failure with death

Hallmark

less • Albumino-cytologic dissociation of CSF

• Increased CSF protein concentration with only modest increase in cell count.

Treatment

(49)

• Respiratory support, may require intubation

• Plasmapheresis

• Intravenous immune globulins

Headache 2/2 Sinusitis

339

Pt usually presents with purulent nasal discharge, stuffiness, facial pain over the sinuses that is worsened by bending down or applying pressure over the affected sinus. Maxillary sinuses are most commonly affected → can sometimes mimic the pain of dental caries.

less • in cases of chronic sinusitis, pain and headache are mild or

absent

Edema of the mucosal lining of the paranasal sinuses 2/2 inflammation leading to obstruction of the sinus opening and accumulation of sinus secretions

Causes: URI, allergies (less common: polyps, foreign body, deviated septum)

less • Strep pneumo, H flu and common culprits in acute sinuisitis

Diagnosis: Clinical diagnosis in most cases. In complicated

cases, can consider CT scan of sinuses if surgery is considered

Treatment:

• Acute sinusitis: decongestants and saline nasal spray • Can use anti-histamines and nasal steroids if suspecting

allergic sinusitis

• Chronic sinusitis: abx: broad spectrum penicillinase-resistant antibiotic. May also need endoscopic drainage.

(50)

Phakomatoses (Neurocutaneous

Syndromes)

339

Phakomatosis incidence: NF (neurofibromatosis) > TS (tuberous sclerosis) > SWS (Sturge-Weber syndrome)

less • Inheritance:

- NF: autosomal dominant with variable expression - TS: autosomal dominant

- SWS: sometimes due to somatic mosaicism, other times due to sporadic mutation

• NF type 1: associated with mutation of a tumor suppressor

gene called neurofibromin(which inhibits the p21 ras

oncoprotein) on chromosome 17 ∴ overactivity of ras may cause some of the manifestations of NF type 1

• NF type 2: associated with mutation in a tumor suppressor

gene called merlin (a critical regulator of contact-dependent inhibition of proliferation) on chromosome 22

• TS: associated with mutations of two genes:

- TSC1 gene (chromosome 9) — codes for a protein

called hamartin, which regulates the cell-cycle, neuronal synapse formation and axon development

- TSC2 gene (chromosome 16) — codes for a protein called tuberin, which has GTPase-activating activity and regulates protein translation, growth and cell proliferation - hamartin and tuberin form heterodimers