Neurology for Neurosurgeons

Dementia

A.     Testing

1.     Tests used to rule out other forms of dementia:

a.      Thyroid function tests

b.      B12 – megaloblastic anemia and posterior column deficit

c.      syphilis

d.     metabolic (kidney function, electrolyte levels and diabetes)

e.      assess levels of heavy metals (e.g. lead, mercury) and anaemia

f.       thiamine deficiency – Wernicke's (ataxia, ophthalmoplegia and confusion); Korsakoff’s (confabulation and amnesia)

2.     Normal Aging that differs from dementia

a.      Independence in daily activities preserved

b.      Person complains of memory loss but can provide details about incidents of forgetfulness

c.      Maintains previous interpersonal social skills

d.     Normal MMSE

B.     Alzhiemers

1.     Development of multiple cognitive deficits manifested by both

a.      Memory impairment

b.      One (or more) of the following cognitive disturbances:

(i)    Aphasia

(ii)  Apraxia

(iii) Agnosia

(iv) Disturbance in executive functioning (i.e. planning, organizing, sequencing, abstracting)

2.     The cognitive deficits cause significant impairment in social or occupational functioning and represent a significant decline from previous level of functioning

3.     The course is characterized by gradual onset and continuing cognitive decline

C.     Dementia with Lewy bodies

1.     occipital lobe hypometabolism

D.     NPH

·       Order of loss: gait à urinary incontinence à dementia

·       increased ventricular size without persistent elevations in intracranial pressure

Delerium

·       Increased risk in patients with dementia

·       Primary disorder of attention that subsequently affects all other aspects of congnition

·       Often represents life-threatening illness (e.g. hypoxia, sepsis, uremic encephalopathy, electrolyte abnormality, drug intoxication, MI)

·       EEG à pronounced diffuse slowing

Migraine

·       Common Migraine

·       Classic Migraine

o   Common migraine + aura

o   May have H/A with occasional focal neurologic deficits that resolve completely in < 24 hrs (visual most common, somatosensory 2^nd)

·       Complicated Migraine

o   Occasional attacks of classic migraine with minimal or no H/A

o   Complete resolution in < 30 days

·       Migraine Equivalent

o   Neurologic sx (N/V, visual aura, etc.) without H/A

o   Seen mostly in children – usually develops into typical migraine with age

·       Hemiplegic Migraine

o   H/A typically precedes hemiplegia which may persist even after H/A resolves

·       Basilar Artery Migraine

o   Restricted to adolescence

o   Recurrent episodes of neurologic deficit restricted to the vertebrobasilar system

o   Deficits: vertigo (most common), gait ataxia, visual disturbance, dysarthria, followed by severe H/A and occasionally N/A

o   FMH in 86%

Contraindications of triptans

1.     Familial hemiplegic migraine

2.     Uncontrolled HTN

3.     CAD

4.     Prinzmetal angina

5.     Pregnancy

6.     Ischemic stroke

7.     Basilar migraine

Abortive medications

Stepwise approach starting with the cheapest and safest

1.     Simple analgesics (e.g., acetaminophen)

2.     NSAIDs

3.     Ergot derivatives – used when migraines last longer than 48 hours and are frequently recurrent

4.     Triptans (seroronin agonist that acts on the serotonin 1b/1d receptor)

Seizures

·       Phenytoin – DOC for partial seizures

·       Juvenile Myoclonic Epilepsy

o   One of the most common epilepsy syndromes

o   Quick little jerks of the arms, shoulders and occasionally the legs

o   Someones followed by a tonic-clonic seizure in the contet of sleep deprivation or alcohol ingestion

·       Complex partial

o   Most common type of seizure with epilepsy in adults

o   brief episodes of impaired consciousness (minutes), failure to respond to stimuli during the episode, staring spells, automatisms and post-ictal confusion

o   EEG pattern is usually normal

o   Hyperventilation during the EEG cannot stimulate a seizure (unlike petite mal)

·       Absence (petite mal)

o   Brief periods of impaired consciousness (seconds), automatisms

o   no post-ictal confusion

o   Hyperventilation during EEG reveals generalized 3Hz spike-and-wave pattern

Parkinsonism

1.     Primary Parkinsonism

a.      Idiopathic paralysis agitans (IPA) Aka shaking palsy

b.      Pathophysiology

i.       Degeneration of dopaminergic neurons of the substantia nigra pars compacta

ii.     Decreases activity of the inhibitory neurons to the internal globus pallidus

iii.    Increased activity to external globus pallidus

iv.    Cholinergic deficit from loss of cholinergic neurons in the nucleus basalis of meynert

c.      Dx:

i.       Clinical diagnosis needs 2 of 3 cardinal signs

d.     resting tremor

e.      rigidity - test passive ROM

f.       bradykinesia – test active ROM and rapid alternating movements

i.       Signs: Hypokinetic gait, postural instability, finger tapping gets smaller, words get quicker on repitition

ii.     nonmotor sx usually seen first: sleep, olfactory, mood

iii.    orthostasis is usually a later manifestation and a SE of park medications

g.      Rx:

i.   start with MAO-B if only a slight tremor

ii.     Dopamine Agonists (Requip, Mirapex) - younger < 60 yo and slight tremor

iii.    Benztropine

(1)  best for resting tremor in patients less than age 70 (bc anticholinergic SE below)

(2)  improves tremor and rigidity but not much affect on bradykinesia

(3)  Anticholinergic SE: dry skin/mouth, constipation, urinary retention, precipitate acute glaucoma

iv.    Clozapine – used if patients have hallucinations

v.      L-Dopa/Cardbidopa

(1)  best for parkinsons but doesn’t slow disease progression

(2)  increased dose gives size effects: dyskinesias, hallucinations

(3)  on-time – dyskinesias (involuntary movements)

(4)  Off-time – return of Parkinson symptoms

h.     DDx: Essential tremor – symmetric and can involve head

2.     Secondary Parkinsonism

a.      Olivopontocerebellar atrophy (OPCA)

i.       degeneration of neurons in specific areas of the brain – the cerebellum, pons, and inferior olives

ii.     Parkinsonism + prominent ataxia

b.      Corticobasal Degeneration

i.       Rare

ii.     Symptoms

(1)  Parkinsonism

(2)  Alien Hand Syndrome asymmetric jerking of limbs

(3)  Apraxia – inability to

(4)  Sensory cortical dysfunction (apraxia, aphasia)

c.      Progressive Supranuclear Palsy (PSNP)

i.       Triad

(1)  Impaired vertical gaze

(2)  Pseudobulbar palsy (mask-like facies with marked dysarthria and dysphagia, hyperactive jaw jerk, emotional incontinence usually mild)

(3)  Axial dystonia (especially of neck and upper trunk)

ii.     Differentiating from Parkinson’s disease

(1)  Mask facies

(2)  Do not walk bent forward

(3)  Do not have a tremor

iii.    Many falls due to disequilibrium + downgaze palsy

d.     Multiple system atrophy

i.       Shy-Dragger is no longer recognized

ii.     Parkinsonism + autonomic dysfunction (orthostatic hypotension, abnormal sweating, disturbance of bowel or bladder)

iii.    widespread neurological signs (cerebellar, pyramidal, LMN)

iv.    degeneration of the lateral horn neurons of thoracic spinal cord

v.      always consider when a patient with Parkinsonism experiences orthostatic hypotension, incontinence or other autonomic symptoms

e.      Drug Induced

i.       MPTP – byproduct of the synthesis of MPPP (a meperidine analog)

ii.     Prescription drugs

(1)  antipsychotics (Haloperidol)

(2)  metoclopramide

(3)  phenothiazine antiemetics (prochlorperazine)

f.       Structural Lesion to Basal Ganglia

i.       Tumor, abscess, infarct

ii.     Gait disturbance predominates

iii.    Tremor is rare

g.      Posttraumatic – dementia pugilistica

Essential Tremor

·       Autosomal dominant pattern may be present

·       Action tremor (suppressed at rest) in the absence of additional neurologic signs

·       Amplitude of tremors typically increase at the end of goal-directed activities

·       Rx:

o   beta-blockers first line

o   primidone: an anticonvulsant that converts into phenylethylmalonamide and phenobarbital

-        may precipitate acute intermittent porphyria: abdominal pain, neurologic and psych sx

·       DDx:

o   Parkinsons – resting tremor, rigidity, bradykinesia

o   Spinocerebellar ataxia (SCA) – genetic degeneration of the cerebellum; can have hand tremor but patients also have a significant ataxic gain; presents at younger age

o   Intention Tremor (e.g. Cerebellar stroke/lesion)

-        Can differentiate by vignette: Essential will be younger pt with FMH of tremor

-        Cerebellar lesions will be alcoholic or vasculopath with a tremor that gets worse as they get closer to the object

Other Movement Disorders

Akathesia – sensation of restlessness

Dystonia

·       Co-contraction of antagonistic muscles (flexors & extensors) resulting in twisting repetitive movements or abnormal postures

• Types:
• Generalized – DYT1 hereditary dystonia
• Focal – usually associated with a specific tast
• writer's cramp - most common focal, task specific dystonia
• blepharospasm
• cervical dystonia (torticollis) – dystonia of the sternocleidomastoid
• Spasmodic dysphonia
• affects the muscles of phonation
• often tremulous and is commonly misdiagnosed as essential tremor.
• Segmental – multiple muscles
• Drug induced: neuroleptics, metoclopramide and phenothiazine entiemetics
• Meige syndrome
• an adult-onset dystonia  that predominantly involves facial muscles, causing disabling blepharospasm and oromandibular dystonia. 
• Some develop spasmodic dysphonia & dystonia of the neck, trunk, arms, and legs 
• Rx:
• Focal dystonia
• botulinum toxin injections (e.g. Botox)
• Diphenhydramine IV for drug induced
• Generalized Dystonia
• Anticholinergics (trihexyphenidyl (Artane) and benztropine)
• work best in children with primary generalized dystonia
• usually ineffective and poorly tolerated in adults.
• DBS – ventrolateral thalamus and internal pallidum most common targets
• DDx:
• Tourette’s – exhibits both motor & vocal tics
• Chronic Tic Disorders
• Motor or vocal tic, not both. Tics usually start at age 5 or 6 and get worse until age 12. They often improve during adulthood.
• may worsen with excitement, stress, fatigue

Tardive Dyskinesia

• chronic exposure to central dopamine blocking agents (neuroleptics, metoclopramide and phenothiazine entiemetics)
• Dx: Clinical
• Involuntary movement of the oral-buccel-lingual muscles
• Arching spasms of the back and neck
• Rx: tetrabenzene; clonazepam

Myoclonus

• random, sudden movements of a body part caused by brief muscle contractions
• most common movement disorder in the hospital
• Cortical Myoclonus
• abnormal hyperexcitability of the cerebral cortex
• mainly affects the distal upper limbs and face, which reflects the largest cortical representations of these body areas
• It is often focal, but may be multifocal, bilateral or generalized, as a consequence of intracortical and transcallosal spreading of abnormal activity
• Subcortical myoclonus – origin between the cortex and the spinal cord
• Causes
• focal – e.g. asterixis
• generalized
• acute – toxin or systemic illness
• chronic – insidious onset, likely degenerative (e.g. Alzheimer’s)

Gait Disorders

1) Highest level disorders: Cortical-basal ganglia-thalamocortical loop lesions

a)     Absent or inappropriate corrective actions - “falling like a log” on the pull test

b)     Inappropriate interaction with the environment

i)      crossing the lower limbs when walking

ii)    leaning the wrong direction when turning or standing

iii)   sitting askew on a chair or commode

c)     Variable performance - Influenced greatly by the environment and emotion

d)    Hesitation and freezing (“ignition failure”)

2) Middle level disorders: Descending motor pathways, ascending sensory pathways, brainstem, spinal cord, and cerebellar pathways.

a)     High cervical myelopathy: numb clumsy hands, ataxic gait or spastic gait

3) Lowest level disorders: Musculoskeletal, neuromuscular, visual and vestibular deficits.

a)     Lower-level gait disorders are disturbances of gait produced by disease of the muscles, skeleton, peripheral nerves, and peripheral visual or vestibular pathways.

Inactivation of the Cerebellar Nuclei

1) fastigium - severe truncal ataxia with a tendency to fall toward the side of the lesion

2) interpositus - classic intention tremor and extremity ataxia on the side of the lesion

3) dentate - awkward execution of skilled motor movements, particularly those requiring fine motor control.

Balance Disorders produced by unilateral pathology

1.  Frontal lobe lesion: patient falls laterally away from the side of the lesion.  Contralateral limb movements may resemble cerebellar ataxia (Brun's ataxia).

2.  Lesion in lenticular nuclei (putamen and globus pallidus): patient falls backward and laterally away from the lesion.

3.  Ventrolateral thalamic lesion:  patient falls backward and laterally away from the lesion (thalamic astasia).

4.  Pusher syndrome: patient pushes himself away from the lesion due to the misperception that his body tilted toward the lesion.  These patients have lesions in the ventrolateral thalamus and, less commonly, in the insula and post-central gyrus.

5.  Cerebellar lesion (particularly the vestibulocerebellum): patient falls laterally toward the side of the lesion.

6.  Vestibular nucleus lesion: patient falls laterally toward the side of the lesion.

7.  Vestibular neuritis: patient falls laterally toward the side of the lesion

Myasthenia Gravis

·       Thymus involvement – hyperplasia or thymoma

·       50% of ocular MG are seronegative

·       80% of MG patients are Ach antibody negative but have a positive antimuscle specific tyrosine kinase (MUSK) antibody assay

• Neonatal MG
• From maternal antibodies
• Rx: AChE inhibitor (neostigmine)
• Rx:

o   Edrophonium used for diagnosis – will improve weakness

o   Oral anticholinesterase initially

• Tertiary amine cholinesterase inhibitors
• rivastigmine, tacrine, donepezil
• not used in MG because the readily pass the BBB
• used in Alzheimer's disease
• Quaternary amine cholinesterase inhibitors
• pyridostigmine and neostigmine
• do not pass the BBB readily and are useful for myasthenia
• Reversible ChEI - pyridostigmine act for duration of 4 hours
• Irreversible ChEI - parathion, not useful in MG and are of toxicological concern for pesticide and nerve gas exposure

o   Immunouppressive agents

§  Prednisolone – works in 1-2 weeks but long term side effects

§  azathioprine, cyclosporine – take longer to work but less side effects

o   Plasmapheresis or IV IG in seriously ill or myasthenic crisis

o   Thymectomy long term – Ideally for those between puberty and 60 years of age with MG that is not confined to the ocular muscles

·       DDx:

o   Lambert- Eaton – loss of DTRs; myasthenia retains DTRs

o   Both can occur with small-cell lung cancer

·       Cholinergic Crisis

o   over-stimulation at a neuromuscular junction due to an excess of acetylcholine or from the inhibition of the acetylcholinesterase enzyme. 

o   Causes:

§  Too high a dosage of myasthenia gravis drugs

§  Irreversible AChE inhibitors (nerve gas or organophosphates)

• Sx: muscles stop responding to Ach à flaccid paralysis; respiratory failure, increased sweating, salivation, miosis

·       Myasthenic Crisis

o   Endotracheal intubation – if vital capacity falls below 1.4L and/or patients looks in distress

o   Withdrawal of anticholinesterases

• Myasthenic vs Cholinergic crises
• both crises exhibit weakness, respiratory problems, dysphagia
• Cholinergic crisis also exhibits GI hyperactivity and hypersecretions
• Differentiate using edrophonium (tensilon)
• Edrophonium worsens the paralysis caused by cholinergic crisis, but strengthens the muscle in the case of myasthenia gravis

Multiple Sclerosis

·       Signs and Symptoms

o   Visual:

§  optic neuritis - Optic Neuritis - suspect in patient with central scotoma, afferent pupillary defect, swollen optic discs, changes in color perception and decreased visual acuity; associated with ms

§  internuclear ophthalmoplegia

o   Motor: extremity weakness and gait ataxia; spasticity of the Les often due to pyramidal tract involvement

o   Sensory: posterior column involvement often causes loss of proprioception; Lhermitte’s sign (electric sher puock-like pain radiating down the spine on neck flexion) is common

o   Reflex: hyperreflexia and Babinski signs

o   GU Symptoms: urinary frequency, urgency, and incontinence

·       Diagnosis

o   No single clinical feature or diagnostic test is adequate

o   MRI

§  Dawson’s fingers – ovoid lesions oriented perpendicular to the ependymal surface

§  DWI should be normal, however plaques can sometimes exhibit “shine through” so the ADC map must be checked to rule-out artifact

§  IgG bands (oligoclonal bands)

§  Seen on agarose gel electrophoresis of CSF not present in the serum

§  Not specific for MS, and can occur in CNS infections and less commonly with strokes or tumors

·       Treatment

o   Acute exacerbations

§  treatment with IV steroids

§  High dose methylprednisolone used when patients have disabling symptoms

o   Reduce frequency of exacerbations

§  Interferon-beta – decreases the frequency of relapse and reduces disability in patients with the relapsing-remitting form of MS

§  Cyclosporine, methotrexate, mitoxantrone – used in the progressive form of MS

§  Plasmapheresis (may enhance immunosuppression)

§  IV IG (theoretical but not recommended)

§  Glatiramer acetate

·       Decreases frequency and severity of MS exacerbations

·       Synthetic mixture of polypeptides containing random combinations of four amino acids found in myelin basic protein

·       Functions by inducing suppressor T-cells that downregulate the T-cell-mediated immune response to myelin antigens that underlies MS

Acute Disseminated Encephalomyelitis (ADEM)

•    Differentiating from MS: ADEM is a monophasic illness, early onset ataxia, involvement of deep gray matter especially thalami, absence of oligoclonal bands

•    Sx appear suddenly 1 to 3 weeks following viral infection or vaccination and can include headache, N/V, confusion and can progress to obtundation and coma

•    Can have hemiparesis, ataxia, optic neuritis 

•    Csf may have pleocytosis and elevated protein

•    Perivenular demyelination

•    Rx: corticosteroid therapy

Stroke Syndromes

Putamen

·       Most common site of intracerebral hemorrhage (hypertensive hemorrhage)

·       Focal neurological signs suddenly develop and gradually worsen

·       Internal capsule that lies adjacent to the putamen is almost always involved – leads to hemiparesis

·        Other signs include hemi-sensory loss, homonymous hemianopsia, stupor and coma

·       eyes are deviated away fom paralytic side

Cerebellum

·       Account for 16% of intracerebral hemorrhage

·       Ataxia, vomiting, occipital H/A, gaze palsy, facial weakness, no hemiparesis

Brainstem

Medulla

Medial	Lateral
Motor	Ipsilateral pain & temp of face
Touch	Contralateral pain & temp of body
Hypoglossal	Cerebellum
	Vestibular system
	Motor to pharynx/larynx
	Horners

·       Medial Medullary

o   Anterior spinal artery

o   XII nucleus/fibers: ipsilateral flaccid paralysis of tongue

o   Pyramid: contralateral spastic paresis (body)

o   Medial lemniscus: contralateral loss of tactile, vibration, conscious proprioception

·       Lateral Medullary (Wallenberg syndrome)

o   PICA

o   Vestibular nuclei: vertigo, N/V, nystagmus (away from lesion)

o   Inferior cerebellar peduncle: ipsilateral limb ataxia

o   Nucleus ambiguous: ipsilateral paralysis of larynx, pharynx, palate à dysarthria, dysphagia, loss of gag

o   Spinal V: ipsilateral pain/temperature loss (face)

o   Descending hypothalamics: ipsilateral Horner syndrome

o   Spinothalamic tract: contralateral pain/temp (body)

Pons

Medial	Lateral
Contralateral motor	Pain & Temp
Contralateral touch	Cerebellum
Abducens	Vestibular system
	Motor to face
	Hearing
	Horners

·       Medial Pons

o   Paramedial Branches of Basilar Artery

o   Corticospinal tract: contralateral spastic hemiparesis

o   Medial lemniscus: contralateral loss of tactile/position/vibration sensation on body

o   Fibers of VI: medial strabismus

·       Lateral Pons

o   AICA

o   Vestibular nuclei: vertigo, N/V, nystagmus

o   Middle cerebellar peduncle: ipsilateral ataxia

o   Facial nucleus and fibers: ipsilateral facial paralysis…

o   Spinal trigeminal nucleus: ipsilateral pain/temperature loss

o   CN VIII nucleus/fibers: ipsilateral hearing loss

o   Descending sympathetics: ipsilateral Horner syndrome

o   Spinothalamic tract: contralateral loss of pain/temperature

·       Central Midbrain – oculomotor paresis and other CN III dysfunctions are common, and cerebellar ataxia and contralateral hemiplegia

o   Weber – Ipsilateral CN III, contralateral Hemiplegia

o   Benedikt – Ipsilateral CN III, contralateral ataxia

Lacunar Infarct

·       due to microatheroma and lipohyalinosis

Syndrome	Pathology	Presentation
Pure motor hemiparesis (most common)	Posterior limb of internal capsule corticospinal & corticobulbar	Unilateral motor deficit (face, arm, and to lesser extent leg); mild dysarthria NO sensory, visual, higher cortical deficits
Pure sensory stroke	VPL of thalamus	Unilateral numbness of face, arm, trunk, leg Dejerine-Roussy syndrome – Rare thalamic pain syndrome that may develop late
Ataxis-hemiparesis	Anterior limb of internal capsule	Weakness that is more prominent in the lower extremity, along with ipsilateral arm and leg incoordination
Dysarthria-clumsy hand	Basis pontis	Hand weakness, mild motor aphasia, NO sensory abnormalities

ACA Stroke

·       contralateral motor and/or sensory deficits more pronounced in the lower limb than upper

·       urinary incontinence, gait apraxia, primitive reflexes (e.g., grasp, sucking)

·       abulia, paratonic rigidity, emotional disturbance

·       deviation of the head and eyes toward lesion

MCA Stroke

·       contralateral motor and/or sensory deficits (more pronounced in the upper limb)

·       conjugate eye deviation toward side of infarct (frontal eye field, Brodmann area 8)

·       homonymous hemianophia (Meyer’s loop of the temporal lobe)

·       left (dominant) – aphasia

·       right (nondominant) – neglect and/or anosognosia

PCA Stroke

·       homonymous hemianophia

·       left (dominant) – alexia without agraphia

·       visual hallucinations (calcarine cortex)

·       sensory symptoms (thalamus)

·       third nerve palsy with pareses of vertical eye movements, and motor deficits (cerebral peduncle, midbrain)

Internal Carotid Stroke

·       Signs and symptoms of a MCA stroke

·       Visual symptoms, such as amaurosis fugax

Transient Ischemic Attack (TIA)

·       associated symptoms resolve within 24 hours

Eyes look toward stroke and away from seizure. Eyes can look away from hemorrhagic stroke?

Genetic Syndromes

Friedreich ataxia

·       most comon type of spinocerebelar ataxia

·       neurologic (ataxia, dysarthria)

·       skeletal (scoliosis, feet deformities)

·       cardiac (concentric hypertrophic cardiomyopathy)

Spinocerebellar ataxia (SCA)

·       genetic degeneration of the cerebellum; CAG repeat disorder

·       dorsal column, later corticospinal, and sometimes later spinothslamic

·       Initial symptoms usually paresthesias in hands and feet

·       Can progress to sensory loss, gait ataxia and distal weakness in legs 

·       later causes dysarthria, abnormal saccades, probable LMN findings and UMN deficits

·       Dx: DNA confirmation

Other

L5 radiculopathy

·       foot drop from inability to dorsiflex the foot

·       most commonly caused by peripheral neuropathy, trauma or congenital (Charcot-Marie-Tooth disease)

·       peroneal nerve or radiculopathy of any spinal roots that contribute to the common peroneal nerve (L4-S2)

Tarsal Tunnel Syndrome

·       entrapment of the posterior tibial nerve as it passes underneath the flexor retinaculum on the medial aspect of the ankle

·       Sx: dysesthesia and numbness plantar foot

Carotidynia

·       Neurological condition caused by inflammation of the carotids and the vagus

·       Pain localized to the carotid artery distribution in the neck – jaw or neck

·       Dental trauma is a common precipitant

·       Diagnosis is clinical although MRI is sometimes required

Carotid endarterectomy

·       < 60% stenosis – disease can be followed every 6-12 mo with duplex U/S

·       Carotid endarterectomy (CAE) beneficial in preventing stroke

·       CAE  indicated for carotid artery stenosis of 60 to 99% even when asymptomatic

·       complete occlusion (100% stenosis) is a contraindication to surgery

Acute angle closure glaucoma

·       preexisting narrow anterior chamber angle is closed in response to pupillary dilation from medications or another stimulus

·       precipitating factor: dim light, anticholinergic medication, or sympathomimetic medication

NF1

1.  Diagnosis

a.      Six or more café-au-lait spots or hyperpigmented macules ≥5 mm in diameter in children younger than 10 years 

b.      Six or more café-au-lait spots >15 mm in adults

c.      Axillary or inguinal freckles


d.     Two or more typical neurofibromas or one plexiform neurofibroma

e.      Optic nerve glioma

f.       Two or more iris hamartomas (Lisch nodules), often identified only through slit-lamp examination by an ophthalmologist

g.      Sphenoid dysplasia or typical long-bone abnormalities such as pseudarthrosis

h.     First-degree relative (eg, mother, father, sister, brother) with NF1 


2.     Pathophysiology

a.      mutation in or deletion of the NF1 gene

b.      gene product neurofibromin serves as a tumor suppressor

3.     Incidence: 1 in 3000

4.     Findings: Cutaneous, neurologic, and orthopedic manifestations:

a.      subcutaneous and cutaneous neurofibromas

b.      plexiform neurofibromas

c.      Gliomas: pilocytic astrocytomas and low-grade astrocytomas are ommon; diffusely infiltrating astrocytomas are also seen in a subset

d.     GI stromal tumors: lead to bleeding or obstruction

e.      Malignant peripheral nerve sheath tumors (MPNSTs) and neurosarcomas are not uncommon in adolescents and adults with NF1, with an approximate lifetime risk of 10%. 

f.       Hypertension: need to look for pheocromoctoma and renal artery stenosis

NF2 – bilateral acoustic neuromas and cataracts

Restless leg syndrome

·       uncomfortable sensation or urge to move legs, discomfort worse in evening, during sleep and at rest; discomfort alleviated by movement

·       Rx: dopamine agonists (e.g. pramipexole and ropinerole)

HIV

·       HIV-Associated Dementia

o   Earliest sx include difficulty with concentration, attention, and mentation

o   Forgetfulness and personality changes begin to appear

o   Psychomotor dyfunction manifested by poor balance and lack of coordinations follows cognitive dysfunction

o   Myoclonic jerks, postural tremor and bowel/bladder dysfunction later eventually leading to an almost vegetative state

o   No focal neurologic deficits

·       Progressive Multifocal leukencephalopathy – multiple non-enhancing lesions that don’t produce mass effect

·       Primary CNS lymphoma – presence of EBV DNA in CSF is specific; MRI reveals a weakly ring-enhancing mass that is usually solitary and periventricular

·       Toxoplasmosis – multiple, ring-enhancing, spherical lesions in the basal ganglia; positive Toxoplasma serology is common in normal subjects in US and not specific

·       Cryptococcal meningitis

o   Chronic lymphocytic meningitis

o   Increases opening pressure, elevated proteins, pleocytosis, low glucose

o   Organisms detected by india ink

HSV Encephalitis

·       May present cutely (<1 week duration) with focal neurological findings

·       CSF – lymphocytosis, elevated proteins

·       PCR analysis of HSV DNA in the CSF is the gold standard

·       Rx: acyclovir

GBS

·       Sx: initially have paresthesias à ascending weakness à respiratory failure

·       Suspect in anyone with ascending weakness and areflexia

·       Supportive therapy

o   follow vital capacity – risk for ventilator failure increases when VC falls below 1.4 L

o   monitor for autonomic instability

·       DDx: Transverse myelitis

o   Suspect transverse myelitis if LP comes back with increased WBC and increased protein

o   GBS have only increased protein

Tick-borne paralysis

·       progressive ascending paralysis over hours to days

·       normal CSF

Botulism

·       hyporeflexia

·       descending symmetrical weakness

·       best diagnosed by fecal cultures or EMG in infantile cases

Craniopharyngeoma

·       bimodal distribution – childrena nd 55-65 years age group

·       benign suprasellar tumor usually presents with hypopituitarism, headaches and bitemporal blindness

Pseudotumor

·       Impaired reabsorption by arachnoid villi

·       Vitamin A and isotretinoi can predispose

Brain Death

·       Absent brainstem reflexes: cough, corneal and gag

·       Absent oculovestibular reflex

·       No spontaneous breathing when ventilator is turned off for 10 minutes

·       Confirmation by at least two physicians

Motor Neuron Disease

·       Degenerative Diseases

o   Mixed UMN & LMN: amyotrophic lateral sclerosis (ALS)

o   UMN: primary lateral sclerosis

o   LMN: progressive muscular atrophy (PMA) and spinal muscular atrophy (SMA)

Myelitis – aka Acute Transverse Myelitis

·       Etiologies: infectious (polio, viral, fungal), autoimmune (MS), idiopathic

·       Myelitis indicates inflammation of the spinal cord

·       Myelopathy indicates compressive, toxic or metabolic etiologies

·       Sx at the time of maximum deficit (90%+)

o   Sensory deficit or paresthesias

o   Muscle weakness

o   Sphincter disturbance (hesitancy, retention, overflow)

·       Evaluation

o   CSF contained elevated protein or pleocytosis in 62% of patients

o   MRI

·       Rx: high-dose steroids may have some efficacy

Corticosteroid-induced myopathy

·       Acute: diffuse muscle weakness and rhabdomyolysis

·       Chronic: proximal muscle weakness without significant pain

Hypokalemia = muscle weakness, myalgias

Neurosarcoidosis

·       Neurologic involvement of sarcoidosis

·       exaggerated cellular immune response

·       Primarily involves the leptomeninges

·       Sx:

o   May produce multiple cranial nerve palsies

o   Diabetes insipidus is the most common neurologic manifestation

·       Findings

o   ACE abnormally elevated

o   CXR reveals hilar adenopathy

Vascular dysautoregylstory encephalopathy

1. Posterior encephalopathy syndrome (PRES)
• Group of widespread vasogenic brain edema with predominance in the parietal and occipital regions
• Small number go onto infarction
• Associated conditions
• Hypertensive encephalopathy
• Preclampsia
• Infection, sepsis, shock
• Autoimmune disease
• Chemotherapy
• Organ transplantation
• Cyclosporine neurotoxicity
• Rx:  treat underlying cause (i.e. Control HTN, hold immunosuppressive or chemo, delivery of the placenta,  etc.)
2. Uremic encephalopathy
• Symmetric edema in basal ganglia with severe cases developing focal infarcts with or without hemorrhage
• Include
• Uremia
• Glomeruli nephritis
• HUS
• TTP
3. Crossed cerebellar Diaschisis
• Hypo metabolism of cerebellar cortex contra lateral to a cerebral hemispheric lesion
• Theory: due to disconnection of the cerebro-ponto-cerebellar pathways

Vasculitis

• Group of disorders characterized by inflammation and necrosis
• Type of CNS involvement
1. Acute encephalopathy 
2. Seizure
3. Cranial nerve
4. Spinal cord
5. ICH, SAH
• Those that affect the CNS
1. PAN - every organ except lung and spleen 
2. Temporal arthritis
3. Takayasu's
4. Wegener 's
5. Lymphomatoid granulomstosis - rare; affects lungs, skin and CNS
6. Behçet's disease - relapsing ocular lesions and recurrent oral and genitsl ulcers 
7. Isolated angiitis of the CNS

Polymyalgia Rheumatica

·       pain is prominent finding; not weakness

• Aching and morning stiffness in shoulder and pelvic girdle lasting > 1 month
• Rx: low dose steroids or NSAIDs

Fibromuscular Dysplasis

• Renal artery most common involvement; internal carotid 2nd
• Sx: Unilateral headaches

Syncope/Vertigo

A.     Evaluation: passing out (syncope) vs dizziness (vertigo)

B.     Terms

1.     Syncope

a.      Presyncope:  patient feels as if they are going to black out”; manifestation of cardiovascular disease

b.      Cardiogenic syncope

(i)    Acute without any provocation or premonitory sx (e.g. N/V, sweating…)

(ii)  Not associated with change in position

c.      Orthostatic hypotension

(i)    Should be evaluated for with every patient with syncope/vertigo

(ii)  Common causes – dehydration, heart failure, medications (e.g., antihypertensives), Parkinson disease, peripheral neuropathy (e.g., diabetic autonomic neuropathy)

2.     Vertigo: illusionary feeling of head movement

a.      Types

(i)    Central Vertigo – brainstem or cerebellar

(ii)  Peripheral Vertigo – ear canal or inner ear

b.      Vestibular Neuritis

(i)    acute vertigo with horizontal nystagmus beating away from the affected nerve; nystagmus may have a torsional (rotary) component

(ii)  no disturbance of hearing

(iii) Patients are usually able to stand and walk although they commonly veer or stagger toward the affected ear.

3.     Other

a.      Seizure: tongue biting, urinary incontinence

b.      Gait unsteadiness: loss of vestibular, proprioceptive, cerebellar or motor function

c.      Dizziness: sensation of imbalance and unsteadines

d.     Motion sickness: sensory conflict; visual input conflicts with vestibular input

C.     Differential Diagnosis by Age

1.     Elderly

a.      Benign positional vertigo

(i)    nystagmus and vertigo when affected ear is down (as during the Hallpike-Dix maneuver)

(ii)  may exhibit all types of nystagmus depending in which semicircular canal is involved

(iii) Rx: Epley maneuver

b.      Labyrinthine ischemia

c.      Toxic vestibulopathy

d.     Vertebrobasilar ischemia – PICA strokes can mimic peripheral vestibular disease (pseudovestibular syndrome)

e.      Viral labyrinthitis

2.     In Young Adults

a.      Ménière syndrome

b.      Viral labyrinthitis

c.      Traumatic vestibulopathy

d.     Toxic vestibulopathy

e.      Migraine

D.     In Children

a.      Benign paroxysmal vertigo

b.      Migraine

c.      Otitis media

Nystagmus

o   slow phase is to the pathologic side; fast phase pulls eye back to normal

o   Central - Nystagmus changes direction depending on which direction the patient looks

o   Peripheral - nystagmus always in same direction irrespective of where patient looks

o   Stroke is the exception

Concussion

1.     Any patient who experiences loss of consciousness should have a head CT

2.     Sports: only grade 1 should be able to return to play

3.     Postconcussion syndrome (PCS)

a.      90% of patients experience H/A and dizziness for at least a month

b.     30-80% develop PCS

i.       irritability, depression, insomnia, subjective intellectual dysfunction

ii.     peak of sx intensity is 1 week; most pts are sx free by 3 mo

4.     Grading

Grade	AAN System
1 (Mild)	1.     transient confusion 2.     no LOC symptoms resolve < 15 min
2 (Moderate)	As above Symptoms last > 15 min PTA is common
3 (Severe)	Any LOC