Neurology Case Presentation

Dr. M. A. Sofi MD; FRCP (London): FRCPEdin; FRCSEdin

• 19 year old male admitted with acute onset generalized weakness for 1 day duration

• Woke up with diffuse weakness; no anti gravity strength in arms, unable to get out of bed

• Proximal > distal weakness; bilaterally symmetrical

• Denied diplopia, dysphagia, dysarthria, facial droop, drooling or change in level of consciousness

2

Case history

• PMH: similar episode in Feb 2013, admitted to local hospital for 4-5 days, ?? Diagnosed with GBS, ?? treated with plasmapheresis, no LP/ EMG

• PMH: nil significant• Home meds: None• FH: Nil for HTN, migraine, DM, asthma, no similar

problem in family members• SH: denies smoking, ETOH or illicit drug use

3

Case history

• Vitals stable• General physical exam unremarkable• Neurological exam–Mental status: AAO * 3–Speech : fluent with comprehension

intact–CN 2-12: PERRLA, EOMI, normal

facial sensation and symmetry, normal facial strength, hearing intact, equal palatal elevation and tongue midline

4

Physical exam

–Motor: Flaccid tone, motor strength 2/5 proximally and 3-4/5 distally BUE and BLE–DTRs: Normal , planter both down

going–Sensory: Intact to LT/PP/ Vibration

and proprioception –Unable to test for cerebellar

function and gait5

Case history

1. What is the clinical pattern of weakness?

2. What is the anatomical localization?

3. What is the differential diagnosis?

6

Case scenario

• Hb - 14.6, WBC 6.1, Plt count 215• Sodium 143, K 1.3, Chloride 110, BUN

13, Creatinine 0.83, Glucose 151, Calcium 9.3, Magnesium 2.0, Phosphorus 2.4

• CK 493, Aldolase 15.7 (on day 3)• TSH: 2.082, free T3 – 3.8, free T4 – 0.9• Urine electrolytes: unremarkable

7

Labs

• Aggressive Potassium replacement• Started showing improvement in

muscle strength on day 1• By day 2 – strength was 5/5 BUE and

BLE• Diagnosed with familial hypokalemic

periodic paralysis• Discharged with follow up care

8

Hospital course

The skeletal muscle genetic ion channelopathies are a distinct group of diseases caused by mutations which mainly occur in voltage-gated ion channel genes. They can be classified in to 2 categories – non dystrophic myotonias and periodic paralyses.NDMs are a group of conditions characterized by muscle stiffness on voluntary movement due to delayed skeletal muscle relaxation. This group includes :• Myotonia congenita• Paramyotonia congenita • Sodium channel myotonias• (potassium-aggravated myotonias (PAMs)• Myotonia fluctuans• Myotonia permanens • Acetazolamide responsive myotonia

Muscle channelopathies

The NDMs are mainly distinguished clinically from the dystrophic myotonias, myotonic dystrophy types 1 and 2, by the absence of extramuscular systemic involvement.

The periodic paralyses are a group of autosomal-dominant disorders characterized by episodes of flaccid paralysis often triggered by an alteration in serum potassium concentration. They include• hypokalemic periodic paralyses type 1 and 2, • hyperkalemic periodic paralysis and• Anderson Tawil syndrome

Muscle channelopathies

• Hypokalemic:– Thyrotoxic periodic paralysis– hyperaldosteronism– RTA– villous adenoma– cocaine binge– diuretics, licorice, steroids, ETOH

• Hyperkalemic (k>7): – hyporenemic hypoaldosteronism (DM/CRF)– oral K, CRF, chronic heparin, rhabdomyolysis

• Normakalemic: – Guanidine, sleep paralysis, MG, TIA, conversion

11

Periodic Paralysis Secondary

• HypoPP is associated with point mutations in both SCN4A and CACNA1S; however, approximately 10–20% of cases remain genetically undefined. Reduced penetrance in women

• HypoKPP 1 is the most frequent form• 1 in 100,000• Autosomal dominant inheritance pattern• M:F – 3 or 4:1 • Onset: first 2 decades of life

12

Hypokalemic periodic paralysis

• Flaccid paralysis – mild focal weakness to severe generalized weakness

• Occur anytime of the day; more common in morning• Absence of myotonia• Absence of clinical or electrophysiological myotonia is

helpful in distinguishing this disorder from HyperKPP• Proximal > distal weakness; legs > arms• Sparing of facial, ventilatory and sphincter muscles• Lasts several hours to more than a day

13

Clinical features

14

Effects of hypokalaemia on the ECGChanges appear when K+ falls below about 2.7 mmol/l

• Increased amplitude and width of the P wave

• Prolongation of the PR interval

• T wave flattening and inversion

• ST depression• Prominent U waves(best

seen in the precordial leads)

Apparent long QT interval due to fusion of the T and U waves (= long QU interval)

• Frequency: highly variable• Frequency decreases after age 30; may

become attack free in 40s and 50s• Permanent fixed weakness or slowly

progressive weakness more common with HypoKPP1

• Attacks may be preceded by sensation of heaviness and or aching in the low back

15

Hypokalemic periodic paralysis

• Strenuous physical activity followed by rest or sleep

• High carb diet• ETOH consumption• Emotional stress• Concurrent viral illness• Lack of sleep• Medications like beta agonists,

corticosteroids, and insulin16

Precipitating factors

• Serum K < 3.0mEq/L • Serum CK level elevated • EKG changes – U waves, flattening of T waves• Provocative testing - Intravenous glucose

load/ insulin • Electrophysiology– Sensory and motor NCS normal between

attacks– During attacks – small CMAP. Reduced

insertional activity, fibs and positive sharp waves

– No myotonia on EMG– Short/ long exercise test

17

Diagnostic studies

• Reducing exposure to known triggers• Acute treatment – replacement of K• Acetazolamide – prevent attack

recurrence and severity –Acetazolamide may ppt weakness in

HypoK PP2• Dichlorphenamide – no longer

available• Triamterene and spironolactone

18

Treatment

A 38-year-old man, feeling poorly after finishing a marathon, was brought to the medical tent near the finish line. He had run three marathons in the past two years.

He was confused, but not hypotensive; pulse was 130 beats/min; his weight was 4.5 kgm higher than at the start of the race. Electrolyte measurements on site included a serum sodium concentration of 118 mEq/L. The most likely proximate reason for the hyponatremia is:

A. Cerebral salt wasting B. NaCl-wasting nephropathy C. Excessive intake of hypotonic fluid D. Excessive sweating

A 60-year-old man with known lung cancer is seen in follow-up with no major symptomatic changes. His BP is 150/90 mmHg, pulse 86 and regular and he has no edema.

Electrolytes reveal a serum sodium concentration of 125 mEq/L; BUN is 6mg/dl, uric acid is 2.8 mg/dl, and the urine osmolality is 280 mosm/kg. The most likely explanation for the hyponatremia is:

A. Cerebral salt wasting B. Diuretic use/abuse C. SIADH D. Psychogenic polydipsia

The most appropriate therapy for patient #2 is: A. Solute-free water restriction B. DDAVP C. Cortisone D. 5% hypertonic saline

60 Year old presented with recurrent attacks of syncope 1.What does ECG rhythm strip show?

_______2.What treatment is recommended?

________

67 year old man presented with left side hemiplegia

1.Describe CT finding? ___

2.What vascular territory is involved? _____

1.What is the diagnosis? _________

2.What blood test has diagnostic value? _______________

Presented with severe acute pain inability to move foot.

On arrival, he is sweaty, distressed and peripherally cyanosedVital Signs:RR 45/min intercostal recessionTempt 38 deg CBP 180/90 mmHg

Upon arrival, arterial blood gases are taken (on 12L / min of O2):pH 7.15 (7.35 – 7.45)PO2 80 mmHg (80 – 95)PCO2 95 mmHg (35 -45)HCO3 42mmol/L (22 – 28)Base Excess + 17 (-3 - +3)SaO2 90%

A 65 year-old man with severe dyspnoea. The patient has a history of Chronic Obstructive Airway Disease (COAD), with regular use of bronchodilators. He is still a heavy smoker, but has no other relevant past history.

Name 2 abnormalities of blood gas analysis above? 1. ___________2. ___________

THANK YOU

History

• 31yo F w/several months progressive BLL weakness; pain greater in LLE

• Bilateral numbness just above breasts & inferiorly• Muscle aches cramps spasms falls• Urinary incontinence & saddle anesthesia• Constipation 2wks (manual dis-impaction)• No history of spinal operation or trauma• No F/C/N/V

Physical Exam

• Sensory deficit inferior to T1 bilaterally• Decreased rectal tone• Motor: LLE 2/5, RLE 5/5• Increased tone/spasticity• Hyper-reflexia• Babinski: Bilateral up going toes• Gait: Able to stand with assistance; drags LLE,

circumduction

LocalizationWhat are the major symptoms and clinical findings ?

What is the anatomical localization of the lesion?

What is the differential diagnosis?

What investigation are requested?

Sag T1 FS MRI Post Sag T2 MRI

Labs/CSF

• Gram stain & culture: rare monocytes, no organisms isolated

• CSF glucose: 69• CSF protein: 31• Elevated levels of IgG antibodies• Oligoclonal bands: negative

Differential Diagnosis

• TumorAstrocytomaEpendymoma

• Demyelinating lesion:Multiple sclerosisNeuromyelitis opticaTransverse myelitisADEM

H&E Stain Hypercellular neural tissue, vessel with perivascular lymphocytic inflammation.

Diagnosis

• Inflammatory demyelinating lesion• Multiple Sclerosis• No further surgical intervention• Neurology for management of MS• Follow up in clinic 2 months postop– Motor LLE improved – MRI Brain & C-spine

Multiple Sclerosis

• Relapsing-remitting MS (RRMS): Most common 85% of MS initially

diagnosed Partial or total

recovery between attacks

• Secondary-progressive MS (SPMS):

RRMS course, but becomes gradually progressive

Attacks & partial recoveries may continue to occur

Over 60% initially RRMS progress to SPMS in 10 yrs

Multiple Sclerosis• Primary-progressive MS

(PPMS): Progressive from onset Symptoms generally do

not remit Progressive disability

w/o acute attacks15% of MS initially

diagnosed

• Primary-relapsing MS (PRMS): Same as PPMS, but with

acute attacks

Multiple Sclerosis • Clinical: Episodic, relapsing-remitting neurologic symptoms in

a young adult (typically)Neurological symptoms disseminated in time & spaceCommon presentations: monocular visual disturbances

(optic neuritis), paresthesias/weakness (myelitis), incoordination (cerebellar), and/or diplopia (brainstem)

• Labs: Oligoclonal bands positive, MBP elevated– Not specific, new tests improving sensitivity/specificity– Early MS vs Clinically definite– MBP elevated in various disease processes

• MRI: T2 intense foci in white matter (UBOs), juxtacortical (G-W junction involving U-fibers), periventricular lesions, involve corpus collosum (perpendicular extensions)

For dissemination in space (DIS) lesions in two out of four typical areas of the CNS are required:

1. Periventricular2. Juxtacortical3. Infratentorial4. spinal cord

For dissemination in time (DIT) there are two possibilities:A new T2 and/or gadolinium-enhancing lesion(s) on follow-up MRI, with reference to a baseline scan, irrespective of the timing of the baseline MRI OR

Simultaneous presence of asymptomatic gadolinium-enhancing and non-enhancing lesions at any time

ADEMADEM)is another important differential diagnosis of MS.This is a monophasic, immune-mediated demyelinating disease which often presents in children following an infection or vaccination.On MRI there are often diffuse and relatively symmetrical lesions in the supra-and infratentorial white matter which may enhance simultaneously.

There almost always is preferential involvement of the cortical gray matter and the deep gray matter of the basal ganglia and thalami.Here we have axial FLAIR and T2W-images of a young patient with ADEM - notice the extensive involvement of the cortical and gray matter, including thalamus.

Tumefactive MSTumefactive demyelinating lesion (TDL) is defined as a solitary de-myelinating lesion greater than 2 cm. Mass effect and contrast enhancement on neuroimaging make it difficult to distinguish this type of lesion from high-grade gliomas

This patient was a previously healthy 35-year-old woman who presented with new-onset generalized tonic-clonic seizures and headaches. MRI scans showed a large right frontal mass with surrounding edema and a mild midline shift.The patient underwent a diagnostic stereotactic brain biopsy. Low-grade glioma and reactive gliosis were among the likely differential diagnoses. Permanent section showed a demyelinating lesion.

Tumefactive MS

T1-weighted magnetic resonance imaging scan showed a right frontal lesion with midline shift.

Neuromyelitis OpticaThis is a demyelinating disease in which the optic nerves and spinal cord are usually involved.Often there are few T2-lesions in the brain.Think of NMO when there are extensive spinal cord lesions (more than 3 vertebral segments) with low T1-signalintensity and swelling of the cord.On axial images the lesions often involve most of the cord.This is unlike MS, in which the lesions are usually smaller and peripherally located.The clue to the diagnosis is in the AQP4-AB titer 1:1024.

Borderzone infarctiontypically these lesions are located in only one hemisphere, either in deep watershed area or peripheral watershed area. ADEMMultifocal lesions in WM and basal ganglia 10-14 days following infection or vaccination.As in MS, ADEM can involve the spinal cord, U-fibers and corpus callosum and sometimes show enhancement.Different from MS is that the lesions are often large and in a younger age group. The disease is monophasic.

Lyme2-3mm lesions simulating MS in a patient with skin rash and influenza-like illness. Other findings are high signal in spinal cord and enhancement of CN7 (root entry zone).SarcoidSarcoid is the great mimicker. The distribution of lesions is quite similar to MS.

PMLPML is a demyelinating disease caused by JC virus in immunosuppressed patients.space-occupying, nonenhancing WMLs in the U-fibers (unlike HIV or CMV).PML may be unilateral, but more often it is asymmetrical and bilateral.Virchow Robin spacesBright on T2WI and dark on FLAIR.Small vessel diseaseWMLs in the deep white matter. Not located in corpus callosum, juxtaventricular or juxtacortical.In many cases there are also