Neurology Review

1. Neurology Review

2. Dementia • RECENT ADVANCES: • Memantine Beneficial in Alzheimer’s Disease • Antipsychotic therapy and increased mortality in Alzheimer’s Disease.

3. DSM-IV criteria for Dementia • A. development of multiple Cognitive deficits with both • 1. Memory impairment • 2. One or more of the following • Aphasia • Apraxia • Agnosia • Disturbed executive functioning • B. Significant impairment in social or occupational functioning and represent a significant decline from prior • C. Not exclusively during a Delerium

4. NINCDS-ADRDA Criteria for Alzheimer’s Disease • 1. Dementia established by clinical examination and standardized brief Mental Status exam and confirmed by Neuropsychological tests • 2. Deficits in two or more areas of cognition • 3. Progressive worsening of memory and other cognitive functions • Onset between 40 and 90 years old • Absence of other systemic or neurologic disorder sufficient to account for progressive cognitive defects

5. FDA approved Medications for AD • Donepezil • Mild to moderate • Start at 5mg per day, up to 10mg, Titrate 4 – 6 weeks • Nausea, Diarrhea, Abdo pain, sleep disturbance • Rivastigmine • Mild to moderate • Start at 1.5mg bid, up to 3 – 6mg bid, Titrate 6 weeks • N/V, anorexia, dizziness • Galantamine • Mild to moderate • Start 4mg bid, up to 8 – 12mg bid, titrate 8 weeks • N/V, Anorexia, weight loss, diarrhea • Memantine • Moderate to severe • Start 5mg/d, up to 10mg bid, titrate 3 weeks • Hallucinations, confusion, restlessness, anxiety, dizziness, headache, fatigue, constipation

6. Alzheimer’s Disease: Key Points • Normal neurologic exam except for characteristic broad-based cognitive and prominent recent memory impairment • Mild cognitive impairment is most likely a pre-demential stage of AD • Cholinergic augmentation with a centrally acting cholinesterase inhibitor is standard therapy in Alzheimer’s Disease • Moderate to severe disease, memantine modestly improves cognition and global function better than cholinergic augmentation • Vitamin E therapy may help slow progression of AD but is not indicated in patients with mild cognitive impairment or significant cerebrovascular disease.

7. Consensus Criteria for Fronto-temporal Dementia • 1. Insidious onset and gradual decline • 2. Early decline in social interpersonal conduct • 3. Early impairment in regulation of personal conduct • Early emotional blunting • Early loss of insight

8. Criteria of Probable Dementia with Lewy Bodies • 1. Persistent Memory impairment may not occur early but is usually evident with progression. Deficits of attention, frontal-subcortical skills, and visuospatial ability may be particularly prominent • 2. Two of the following core features • a. Fluctuating cognition with pronounced variation in attention and alertness • Recurrent visual hallucinations that a typically well formed and detailed • Spontaneous motor features of parkinsonism • 3. Supportive features include repeated falls, syncope, neuroleptic sensitivity, delusions, other hallucinations, REM behavior disorder

9. Other dementias Key Points • Vascular dementia, Dementia with Lewy Bodies, and frontotemporal dementia most common • A clinical diagnosis of vascular dementia is established by history of stroke risk factors, a stroke-like disease course, and/or findings on imaging. • Dementia with Lewy bodies is characterized by parkinsonism repsonsive to dopaminergic therapy, visual hallucinations, and/or fluctuating cognition • Cholinergic augmentation (rivastigmine) may alleviate psychiatric symptoms a/w dementia with Lewy bodies. • Frontotemportal dementia presents with early executive and personality change and pronounced or asymmetric frontal (and temporal) atrophy on brain imaging • Creutzfeldt-Jakob disease should be suspected in patient with dementia a/w myoclonus that progresses over weeks to months

10. Clinical criteria for probable Creutzfeldt-Jakob Disease • 1. Rapidly progressive dementia • 2. EEG with periodic sharp waves or elevated 14-3-3 protein in CSF • 3. Two of the following • Myoclonus • Visual or cerebellar signs • Pyramidal or extrapyramidal motor signs • Akinetic mutism

11. Headache and Migraine • Primary vs secondary headache • Migraine • (Trigeminal-vascular system) • Tension-type • Cluster (trigeminal autonomic cephalgias) • Other primary headaches

12. Migraine-specific acute Rx • Ergot Derivatives • DHE • Triptans • Sumatriptan • Rizatriptan • Zolmitriptan • Others (Frovatriptan has long half-life)

13. Nonspecific Rx for headaches • ASA • Acetominophen • Fiorinal/fioricet • Midrin • Cafergot • NSAIDs • Antiemetics

14. Migraine rescue • Avoid narcotics • Ativan • Lidocaine • Magnesium • Depakote • Atypical antipsychotics • Solumedrol • Antiemetics IV • Hydroxyzine

15. Migraine prophylaxis • Beta-blockers • Calcium channel blockers • Anticonvulsants • Topiramate • Valproic Acid • Others • Tricyclics • Sansert (not available) • Periactin • Coenzyme Q10 • Vitamin B2 • Magnesium

16. Headache Keypoints • Migraine headaches originate in the brainstem and higher brain structures that cause pain coming from inflamed cerebral blood vessels • Acute migraine Rx includes specific therapy with triptans or ergots • Triptans are contraindicated in patients with significant coronary risk factors or a history of coronary disease • Rx of migraine should be administered as early as possible in the attack to ensure the greates efficacy using the lowest dose of therapy • Prophylactic migraine Rx is indicated in patients who experience more than 2 days with headache per week. • Proper sleep hygiene may be the most effective migraine prophylaxis • Consumption of foods containing tyramine, nitrates, dairy products, and xanthines may trigger migraine is some people • Menstrual migraine prophylaxis includes administration of low-dose estrogen therapy during menstruation, continuous estrogen therapy increased during menstruation, or oral magnesium

17. Medication overuse Keypoints • Patients who use pharmacologic therapy for headache more than 2 days per week are at risk for medication overuse headache • Management of medication oversuse headache includes migraine prophylaxis and complete withdrawal of the medication of overuse.

18. Other headache Keypoints • Immobility increases cluster headache pain, whereas increased movement exacerbates migraine • Patients with cluster headache may benefit from high dose corticosteroid therapy administer for 2 – 4 weeks with taper over 2 – 4 weeks • Primary sleep disorder should be excluded in all patients with chronic headache syndromes.

19. Headache eval - Keypoints • LP should be performed in patients with headache only after CT or MRI excludes mass lesion or hydrocephalus • Temporal artery Bx is the study of choice for Dx of GCA • High-dose corticosteroid therapy is indicated in GCA • If untreated, GCA may cause blindness

20. More headache Keypoints • Idiopathic intracranial hypertension (pseudotumor cerebri) may present with disabling headaches and has potential risk for blindness • Patients with tirgeminal Neuralgia may benefit from therapy with anticonvulsants and baclofen • Surgical decompression of the trigeminal ganglion may be beneficial in refractory trigeminal neuralgia

21. Movement Disorders • Recent Advance: Long term efficacy of deep-brain stimulation in Parkinson’s Disease

22. Classification of Parkinsonism • Primary Parkinsonism • Secondary Parkinsonism • Medications • Hydrocephalus • Infections • Metabolic • Neoplastic • Psychogenic • Toxin • Traumatic • Vascular • Parkinsonism-Plus Syndromes • CBD • Dementia syndromes • Multiple System Atrophy • PSP • Hereditary and Degenerative Parkinsonism • Familial basal ganglionic calcification • FTD linked to Chromosome 17 • HD • Wilson’s Disease • Fragile X premutation carriers • others

23. Rx of Parkinson’s Disease • Amantadine • Apomorphine* • Carbidopa-levodopa • Entacapone (COMT inhibitor, in Stalevo) • Dopamine agonists • MAO-B inhibitors (Rasagaline) • Anticholinergics (Trihexyphenidyl)

24. Treating PD • If no functional impairment: Neuroprotective Rx • Antioxidants, Co-10, Azilect, Glutamate Antagonists, creatine • If tremor predominant: Amantadine or anticholinergic • If not tremor dominant and < 70: Dopamine agonist, Sinemet, Amantadine, Azilect • > 70 years old; Sinemet, MAO inhibitors

25. PD Keypoints • In 75% of patients, rest tremor is first motor manifestation • Rigidity in PD may manifest as either cogwheeling or lead-pipe rigidity • Management of patients >70 with new Dx involves not inducing or exacerbating cognitive impairment • L-dopa is the most potent agent currently available to control symptoms in all age groups • Carbidopa with L-dopa decreases likelihood of peripheral dopaminergic effects • Early dopamine agonist Rx is recommended in patient with PD < 70, early Rx with Sinemet is recommend >70 • Anticholinergic agents may help with tremor and rigidity but are typically indicated only for younger patients without signs of dementia • Surgical procedure of choice is deep-brain stimulation of the subthalamic nucleus • Surgery may benefit younger patients who respond well to Sinemet but continue to experience significant periods of medication inefficiency and dyskinesias despite optimal treatment.

26. Movement Disorders misc • Drug induced parkinsonism • Antiemetics etc • Dystonias • Essential Tremor • Propranolol, Mysoline, Neurontin, Topiramate • Huntington’s Disease • Restless Leg Syndrome • Check for Iron deficiency

27. Multiple Sclerosis • Most common cause of non-traumatic neurologic disability in young adults • Signs/Symptoms • Diagnosis • Course • DDX • Cervical spondylosis, myelopathies, DM, neurosarcoid, SLE, Sjogren’s, Vit B12 deficiency • NMO

28. MS cont’d • Rx exacerbations • Disease modifying Therapies • Interferons • Glatiramer • Natalizumab (blocks migration of inflammatory cells, a/w PML • Mitoxantrone • Other immunosuppressants • Symptomatic Rx

29. MS keypoints • On MRI, the presence of ovoid lesions perpendicular to the lateral ventricles and corpus callosum are characteristic of MS • Management of leg spaciticity a/w MS should involve PT for stretching and pharmacologic Rx • The decision to treat an exacerbation of neurologic deficit with corticosteroids is determined by whether the patient’s function is affected • Plasma exchange may benefit patients with severe exacerbations of MS that are refractory to steroids • PT, OT, ST may be appropriate after severe MS exacerbations • There is no therapy that convincingly slows degenerative processes in MS or definitively provides neuroprotection. • Treatment of primary progressive MS is limited to symptomatic Rx

30. Peripheral Neuropathies • Recent advance: Muscle-specific Kinase antibodies in Myasthenia Gravis • Axonal vs Demyelinating • Acquired vs hereditary • Charcot-Marie-Tooth disease is most common hereditary neuropathy • Toxins

31. Neuropathies a/w pain • Cryptogenic Sensorimotor neuropathy • Diabetic Neuropathy • Vasculitis • GBS • Radiculopathy/plexopathy • Alcoholic neuropathy • HIV sensorimotor Neuropathy • Syphilis • Heavy Metal toxicity • Amyloidosis • Fabry’s disease • Hereditary sensory/autonomic neuropathy

32. Peripheral Neuropathy eval • Standard: • CBC, Chemistries, SPEP/IFE, B12, glucose assessment, RPR, TFTs • Optional: • HIV, ESR, ANA, RF, SS-A, SS-B • Anti-Hu • Genetic studies • Lyme titre • Heavy metals – 24 hour urine • Phytanic acid • LP if suspecting CIDP or AIDP • NCVs • Sensory nerve Bx • If vasculitis suspected

33. Symptomatic Rx of Neuropathic pain • TCAs • AEDs • Lidocaine Patch • Capsaicin cream • Acupuncture • Transcutaneous nerve Stim • Tramadol

34. Guillain-Barre • Rapidily progressive, immune-mediated demyelinating polyneuropathy • Up to 75% a/w preceding infection, immunization, or surgical procedure • EBV, CMV, Campylobacter, Lyme, Hepatitis, HIV • Weakness, pain, paresthesias, autonomic symptoms, facial weakness, ophthalmoparesis, respiratory failure (25%) • 2 – 4 weeks • Respiratory monitoring – FVCs etc • EMG • Rx: IVIG or Plasmapheresis

35. Polyneuropathy keypoints • Asymmetric involvement should raise suspicion for MND, radiculopathies, plexopathies, compressive neuropathies, or mononeuritis multiplex • Viral illness, immunization, or surgery may precede GBS • DDX of neuropathy with Mental Status change should include B12, thiamine, or niacin deficiency • Immunosuppresive Rx indicated for CIDP • NCV may be helpful to determine Axonoal vs demyelinating process • Treatment of idiopathic polyneuropathy generally limited to pain Rx • Hospitalize and do frequent respiratory monitoring for suspected GBS • Rx with IVIG or plasmapheresis GBS patients who are unable to ambulate independently and have impaired respiratory functions or rapidly progressive weakness • Oral immunosuppressive rx for CIDP; IVIG or plasmapheresis indicated for severe or refractory CIDP

36. Amyotrophic Lateral Sclerosis • ALS – both UMN and LMN • Primary Lateral Sclerosis – UMN • Primary Bulbar palsy – Brain stem • Progressive muscular Atrophy – LMN • ~2/100,000 incidence. • Slight male predominance • 95% sporadic • Mean survival 2 – 5yrs

37. Rx of ALS • Riluzole is approved for ALS (very modest effect) • PEG • Noninvasive PP ventilation with Bilevel positive airway pressure may prolong survival and improve quality of life • Symtomatic Rx for spasticity, emotional lability, muscle cramping, and drooling may maintain dignity and quality of life

38. Myasthenia Gravis • Antibodies against the AChR • Characterized by fatigable weakness • Ocular with diplopis, ptosis • Bulbar with dysarthria, dysphagia • Proximal extremity • Neck with head drop • Respiratory with dyspnea • Dx: repetitive Nerve Stim, Tensilon (not availbable) or SF-EMG may help • Rx: Mestinon, immune Rx • May initially get worse on Prednisone

39. Medications to avoid in MG • Calcium channel blockers • Beta-blockers • Quinine • Quinidine • Procainamide • Lidocaine • Aminoglycosides • Polymyxin • Morphine • Barbiturates • Neuromuscular blocking agents • Magnesium

40. MG keypoints • There is an increased incidence of thymic abnormalities and thyroid disease in patients with MG • 85% of patients with generalized MG are AChR antibody positive • Mild cases may be treated with acetylcholinesterase therapy (pyridostigmine 60mg tid or qid), whereas worse presentations may benefit from immunosuppresive Rx • IVIG or Plasmapheresis may help severe weakness

41. Myoglobinuria • Prolonged intensive exercise • Viral and bacterial infections • Drugs and toxins (EtOH!) • Neuroleptic Malignant syndrome • Heatstroke • Severe metabolic disturbance • Inflammatory myopathies (rare) • Limb-girdle muscular dystrophy • Metabolic Myopathies • Ex) Myophosphorylase deficiency)

42. Myopathies presenting in Adulthood • Muscular dystrophies • Inflammatory Myopathies • Polymyositis, dermatomyositis, IB myositis, HIV • Metabolic Myopathies • Acid maltase deficiency, lipid storage disease, etc • Mitochondrial Myopathies • Endocrine Myopathies • Toxic Myopathies • EtOH, corticosteroids, etc • Myotonic dystrophy • Distal Myopathies

43. Myopathies- key points • Myoglobinuria may manifest with exercise-induced weakness and myalgias and cola-colored or red urine • Many familial – family history • Cardiac disease a/w myotonic dystrophy and some muscular dystrophies • FVC and Max inspiratory pressures monitoring • CK most useful lab test • CK elevated also in muscle trauma, viral conditions, seizures, stenuous exercise, and some medications • Benign elevated CK may occur in African American Population, some muscular patients, and hereditary. • Molecular genetic testing may avoid muscle BX • CK and EMG are normal in corticosteroid induced myopathy • Critical illness myopathy commonly occurs in setting of Rx with corticosteroids and NM blockers

44. Brain tumors etc • Temozolomide for GMB is new • Meningiomas most common in peri- and post-menopausal women • Radiographic and clinical observation usually OK for small, asymptomatic meningiomas • CT scan in meningiomas: extra-axial calcified mass with homogeneous enhancement • MRI more sensitive for meningiomas bu less reliable for showing calcium • Surgical resection recommended for symtomatic mengiomas • Focal radiation for unresectable, recurrent, or anaplastic meningiomas • Most gliomas in adults are high grade and incurable • Resection and XRT indicated for most high-grade gliomas, whereas chemotherapy may benefit younger patients with good performance status.

45. More tumor stuff • Primary CNS lymphoma occurs infrequently in immunocompenent patients, but is relatively common in immunocompromised patients • Aggressive resection for primary CNS lymphoma is not indicated • Chemotherapy usually followed by XRT is indicated for immunocompetent patients with primary CNS lymphoma. • Lung, breast, and melanoma are most common solid tumors to metastasize to the brain • Have high index of suspicison • Rx: Steroids for vasogenic edema, XRT for multiple mets, surgery for solitary met • Paraneoplastic Syndromes: • Limbic encephalitis, cerebellar degeneration, sensory neuronopathy, opsoclonus-myoclonus, LEMS • anti-neuronal antibodies

46. Epilepsy • Partial vs Generalized Seizures • Localization related vs primary epilepsies • Optimize monotherapy • Surgery may be effective for medically intractable localization-related epilepsy • Medications • Status Epilepticus

47. Stroke • See separate presentation