Worsening Weakness and Numbness

Question 1

Helen, 29, presents with painless numbness in lower limbs

PHx: non significant

Smoker, occasional alcohol, no illicit drugs

FHx: mother has Graves disease

Social: full time pharmacy assistant, just married

What other questions would you like to ask?

Answer 1

Location of numbness (including sensory level)

Course

Onset

Duration

Other symptoms (e.g. visual disturbance, bowel and bladder symptoms including frequency, urgency and incontinence)

Question 2

Helen, 29, presents with painless numbness in LLs

Started under L foot, moved up L leg and progressed to ribcage

Gradual increase in intensity and extent over 2 weeks

Other Sx: less severe numbness in R leg/foot, mild bilateral leg weakness, “can’t walk properly, worse in evenings, after my shower/bath”

Other questions on systems review? Why are you asking each of these?

Answer 2

Back pain, trauma

Sx not worse wih cough/sneeze or valsalva: suggests compressive aetiology (e.g. root lesion, any pathology causing an underlying acute back pain) which is exacerbated by increased intrathoracic pressure

Systemic AI disease

Rashes or arthralgia: SLE (usually a brain problem, doesn’t affect rest of CNS)

Miscarriages: anti-phospholipid syndrome

Dry mouth, dry eyes: Sjogren’s syndrome

Recent infections: para-infectious causes, GBS

Recent vaccinations: GBS

Diet restriction (esp veganism): B12 deficiency

B symptoms/paraneoplastic syndromes: malignancy

Question 3

How can Sjogren’s syndrome affect the CNS?

Answer 3

Can produce inflammatory change in spinal cord

Question 4

What paraneoplastic syndromes can affect the CNS?

Answer 4

Paraneoplastic cerebellar degeneration (typically in small cell lung cancer), causing ataxia

Peripheral neuropathy (chronic sensorimotor neuropathy)

Question 5

Helen, 29, presents with painless numbness in LLs

Started under L foot, moved up L leg and progressed to ribcage

Gradual increase in intensity and extent over 2 weeks

Other Sx: less severe numbness in R leg/foot, mild bilateral leg weakness, “can’t walk properly, worse in evenings, after my shower/bath”

Where in the nervous system could the problem be?

Answer 5

Hx very compatible with inflammatory cord disorder due to the age of the patient and the fact there is no associated pain around the likely affected region

Problem is in spinal cord; brain or peripheral nerve disorder would not affect one side of trunk up to a specific level

Question 6

Helen, 29, presents with painless numbness in LLs

Started under L foot, moved up L leg and progressed to ribcage

Gradual increase in intensity and extent over 2 weeks

Other Sx: less severe numbness in R leg/foot, mild bilateral leg weakness, “can’t walk properly, worse in evenings, after my shower/bath”

Summarise these Sx

Answer 6

Paraparesis with sensory level

Heat sensitive symptoms

Question 7

Uhthoff’s phenomenon

Answer 7

Reversible and stereotypic decrements in physical and cognitive Sx due to increased ambient body temperature (including exercise, fever, summer, hot showers)

Relatively specific for MS

Question 8

Lhermitte’s sign

Answer 8

Electrical sensation that runs down the back and into the limbs, elicited by bending the head forward

Question 9

Describe a simplified approach to determining the anatomical cause of sensory loss

Answer 9

Question 10

Describe a simplified approach for localisation of the cause of neurological symptoms

Answer 10

Question 11

What are 3 clinical features suggestive of a spinal cord pathology over a peripheral neuropathy?

Answer 11

Sensory level

Hyperreflexia

Bowel and bladder problems

Question 12

What are 2 clinical features suggestive of a peripheral neuropathy over a spinal cord pathology?

Answer 12

Glove and stocking, dermatomal or single nerve distribution

Loss of reflexes

Question 13

DDx for subacute paraparesis

Answer 13

Spinal cord pathology: MS, tumour

Peripheral nerve lesions: GBS (acute demyelinating polyradiculopathy)

Question 14

What features of Helen’s case are not consistent with GBS as an underlying cause?

Answer 14

Classically no sensory loss (and would not have a sensory level)

Weakness pattern usually distal in UL and proximal in LL

Weakness is the primary feature

Question 15

DDx for acute paraparesis

Answer 15

Trauma

Spinal cord stroke or SAH (usually in people with advanced arteriopathy)

Question 16

What is the cardinal feature of spinal cord stroke?

Answer 16

Rapid weakness but preservation of dorsal column function, because stroke almost always involves the anterior spinal supply

Question 17

Helen, 29, presents with painless numbness in LLs

O/E: normal cranial nerve examination, normal UL examination, LL examination revealed few beats of clonus at L ankle, mild pyramidal pattern of weakness in both legs (worse on the L), brisk reflexes, upgoing plantar responses, loss of light touch and vibration up to T4, anal sphincter tone normal

Localise the lesion

Answer 17

UMN signs with a sensory level confirming this is in the spinal cord above or at T4

Question 18

Helen, 29, presents with painless numbness in LLs

UMN signs with a sensory level confirming this is in the spinal cord above or at T4

Ix?

Answer 18

MRI cervical and thoracic spine (lumbosacral goes from conus medullaris downwards as the spinal cord has already finished at this level; the conus is included in the thoracic anyway)

Somatosensory evoked potentials (SEPs)

Lumbar puncture: look for evidence of an inflammatory process (in MS: presence of oligoclonal bands in CSF and absence in blood serum, in neuromyelitis optica: anti-aquaporin Abs)

Question 19

Neuromyelitis optica

Answer 19

Neuromyelitis optica (NMO), also known as Devic’s disease or Devic’s syndrome, is a heterogeneous condition consisting of the simultaneous inflammation and demyelination of the optic nerve (optic neuritis) and the spinal cord (myelitis)

Can be monophasic or recurrent

Question 20

What does Helen’s MRI show?

Answer 20

Ovoid inflammatory lesion in the cervical cord (“plaque”)

Confirms the Dx of a partial transverse myelitis

Question 21

What is inflammatory myelitis?

Answer 21

Inflammatory demyelination of segment(s) of spinal cord

Functionally transects the cord

Question 22

Causes of transverse myelitis

Answer 22

MS (common)

Infectious/parainfectious inflammation (HSV, EBV, VZV, syphilis, Lyme)

Other AI disorders (vasculitis, systemic AI diseases)

No specific aetiology (40%; prognosis usually good so long as brain looks okay on imaging and there is no Hx of demyelinating lesions in the brain that would suggest MS)

Question 23

Possible complication of VZV infection in immunosuppressed patients

Answer 23

Necrotising myelitis (in association with shingles)

Question 24

Helen has an MRI brain performed

CSF: protein 0.38 g/L (N 0.15-0.40), cells 4/uL (3 lymphocytes and 1 erythrocyte; N), glucose 3 mmol/L (N), OCBs positive (without corresponding IgG in the serum)

Visual evoked potentials: normal

What are OCBs? Are these results in keeping with a transverse myelitis?

Dx?

Answer 24

Oligoclonal bands represent immunoglobulin produced by clonally expanded plasma cells; if not present in the blood serum, this indicates that a subpopulation of Abs have been created inside the intrathecal space and this is a specific finding for CNS inflammation/infection

Consistent with a transverse myelitis (cells may be mildly elevated)

Dx: clinically isolated syndrome (CIS) of MS (first clinical presentation compatible with the Dx of MS but not fulfilling the MS diagnostic criteria)

Question 25

What are the 4 most common first presentations of MS?

Answer 25

Transverse myelitis Optic neuritis Brainstem/cerebellar presentations (ataxia, nystagmus, vertigo, diplopia) Incidental or with fatigue/non-specific Sx (nowadays more common)

Question 26

How is MS diagnosed?

Answer 26

Dissemination in space in the CNS: presence of documented neurological symptoms/signs in at least 2 functional systems of the CNS (e.g. transverse myelitis AND optic neuritis), as supported by radiological findings (lesions in at least 2 regions of the CNS) Dissemination in time: at least 2 relapses at least 1 month apart, with at least 2 lesions of different age on imaging

Question 27

DDx for MS

Answer 27

Neuromyelitis optica (NMO, Devic's disease) Other systemic AI diseases Acute disseminated encephalomyelitis (ADEM) Sarcoidosis Infections (e.g. brain abscess) Tumours Conversion disorder, somatisation

Question 28

Acute disseminated encephalomyelitis

Answer 28

ADEM is a rare AI disease marked by a sudden, widespread attack of inflammation in the brain and spinal cord Can be post-viral, post-vax

Question 29

Causative organisms for brain abscess

Answer 29

GAS Nocardia

Question 30

What is the most common presentation of systemic sarcoidosis?

Answer 30

Pulmonary involvement (SOB, cough, fatigue)

Question 31

Characteristic appearance of sarcoidosis on XR

Answer 31

Bilateral hilar lymphadenopathy (bilateral enlargement of LNs of pulmonary hila); describes the enlargement of mediastinal LNs and is most commonly identified by a CXR

Question 32

What is a cold abscess?

Answer 32

A patient with a cold abscess does not appear systemically unwell

Question 33

What factors are predictive for a second attack of MS?

Answer 33

High predicted by number of inflammatory lesions on baseline MRI brain (Helen had 1 spinal and several brain lesions) Presence of OCBs in CSF confers additional risk

Question 34

What is MS? Describes its epidemiology, pathogenesis, presentation and natural Hx

Answer 34

AI demyelinating disease of the CNS Most common neurological disease affecting young people in Aus Characterised by inflammation, demyelination and axonal degeneration Neurological Sx can be inflammatory (acute) and degenerative (chronic) Course usually relapsing and remitting, usually followed by secondary progression

Question 35

Describe the 3 main subtypes of MS

Answer 35

Relapsing-remitting MS (RRMS; most common): relapses with complete or incomplete recovery and stable phase between relapses Secondary progressive MS (SPMS): 50-75% of RRMS cases become SPMS within 15 years, gradual neurological deterioration, with or without superimposed relapses Primary progressive MS (PPMS; 10%): gradual but continuous neurological deterioration, if relapses occur it is called progressive-relapsing MS

Question 36

What factors are suggestive of a better prognosis in MS?

Answer 36

Female, young (onset before 35) Initial sensory Sx and optic neuritis (as opposed to motor or cerebellar dysfunction) Initial mono-symptomatic presentation Sudden onset, good recovery, lower attack rates, longer attack intervals

Question 37

Describe the natural Hx of MS

Answer 37

1/3 do well without accumulating significant disability 1/3 accumulate neurological deficits to impair activities but not serious enough to prevent them from leading a normal life 1/3 become disabled and require gait/mobility aids and even high level care

Question 38

Helen's numbness improves without treatment over 3/52 10/12 later: pain behind the L eye worse with eye movement, visual acuity reduces from 6/5 baseline to 6/9 (two lines on acuity chart), colour desaturation in L, papilloedema in L on fundoscopy How can colour desaturation be assessed? Dx?

Answer 38

Ishihara plates, or ask patient to cover bad eye, show them something red, then ask them to swap eyes and see if there is any reported difference Dx: acute optic neuritis (this second attack or relapse confirms her Dx of clinically definite MS)

Question 39

How is MS relapse defined? What is the prognosis of a relapse?

Answer 39

Episode of neurological disturbance consistent with MS which lasts for at least 48 hours (but usually 2-4 weeks; note the 48-hr cut-off is a research definition and patients may report shorter episodes) and occurs at least 30 hours from onset of last attack; is not preceded by a viral-like illness Usually there is good recovery but residual disability may persist

Question 40

Mx of MS relapse Why can't an oral at-home option be used?

Answer 40

3-5/7 of IV methylprednisolone 1g/day to reduce severity of attack and shorten recovery time (although effect on ultimate recovery is uncertain Also give prophylactic slow K Oral prednisolone has not be shown to work in this clinical context, although it has recently been demonstrated that large doses of oral methylprednisolone may be effective (but not generally used)

Question 41

SEs of IV methylprednisolone

Answer 41

Agitation (sleep disturbance, psychosis, mania) Hypokalaemia (give prophylactic slow K!) HTN Hyperglycaemia Peptic ulcer disease (esp if also on NSAIDs) Body fat redistribution ("moon face") OP AVN Cataracts Skin changes Increased infection risk (immunosuppression)

Question 42

Following the course of steroids, Helen's acute optic neuritis subsides; her retrobulbar pain resolves, her visual acuity recovers to 6/7.5, her colour vision recovers to normal and fundoscopy shows a pale optic disc in her L eye Significance of pale optic disc? Long term MS Mx?

Answer 42

Pale optic disc indicates optic atrophy Long term MS Mx: no cure so disease modifying therapy is the mainstay of treatment Goals of treatment are prevention of relapses and/or new MRI lesions, and prevention of disability progression

Question 43

List disease modifying therapies currently available for the treatment of MS

Answer 43

1st tier: interferons B (SC or IM injections 1-4/week), glatiramer acetate (daily SC injections), teriflunomide (daily tablet) 2nd tier: fingolimod (daily tablet), dimethyl fumarate (BD tablet) 3rd tier: natalizumab (monthly infusion), alemtuzumab (2 infusion courses over 5 years)

Question 44

Common presentations of MS relapses (in descending order of incidence)

Answer 44

Sensory Pyramidal Visual Brainstem Cerebellar Sphincteric Cognitive NB A Hx of certain relapse presentation predisposes patients to experiencing simiar relapses in the future (i.e. relapses tend to recur)

Question 45

What is pyramidal weakness?

Answer 45

Predominantly flexion weakness in LL (hip flexion, knee flexion, ankle dorsiflexion) or extension weakness in UL

Question 46

Common permanent MS symptoms

Answer 46

Fatigue Walking difficulties Bowel and bladder symptoms (frequency, urgency, incontinence) Pain and other sensations Visual disturbances Cognitive problems Tremors Sexual dysfunction Inability to work Depression (reported by 14% of patients; suicide is 7-14x more common than general population)

Question 47

One year later, Helen's disease has remained stable with no relapses, no new symptoms/signs and no new lesions on her brain and spine MRI However she has been depressed for the past 3/12, with loss of interest in her usual hobbies, poor social life and insomnia Mx of Helen's depression?

Answer 47

Start symptomatic therapy with SSRI (e.g. escitalopram 10mg daily) OR commence psychotherapy (insufficient evidence to support combination therapy of depression)

Question 48

Possible social consequence to consider in a young person with chronic illness

Answer 48

Relationship changes Financial Demands at work, diminished employment opportunities Study Wanting children, fertility (consider medication SEs), sexual dysfunction Young family Adjustment, grief, fear of unknown Low self esteem Independence vs care needs

Question 49

In Helen's 30s, she has 2 minor relapses over next 10 years, including an episode of diplopia and mild imbalance lasting 2/52, and L LL numbness and weakness again for 1/12 Receives 2/52 inpatient rehab program and DMT is changed to fingolimod What parties are required for effective multidisciplinary Mx of MS?

Answer 49

Neurology Rehab physicians Continence/urology Pain Psychology Patient support groups (MS society)

Question 50

What kinds of supports does formal rehab provide?

Answer 50

Symptomatic and supportive therapies: multidisciplinary involvement (medical, nursing, PT, OT, ST, psychology, SW) May be inpatient or outpatient/community-based Problem-solving education process

Question 51

What are the goals of rehab in MS?

Answer 51

Improve/maintain functional independence (transfers, mobility, personal care) Modify environment and adaptive equipment Addressing psychosocial and environmental factors Caregiver education and support (reduce burden of care)

Question 52

How can fatigue be managed in MS?

Answer 52

Education: avoid heat, consider air conditioning, adequate sleep, good hygiene, good diet, adequate exercise OT: teach pacing and work simplification strategies, provide equipment to minimise effort and energy consumption, involve employer to work on flexible work hours or work at home options, transportation (OT driving assessment), accessible work environment (e.g. location of bathrooms), memory aids, air conditioning PT: aids for walking to improve gait efficiecny, home exercise program to improve fitness and aerobic capacity/endurance, improve well-being Medication options include amantadine and modafinil

Question 53

Helen retires early (40-50s) due to deterioration in gait and repeated falls (experiences weakness, spasticity, ataxia/incoordination, imbalance, fatigue) Dx? Mx?

Answer 53

Secondary progressive MS Cease fingolimod (no evidence of effect of disease-modifying therapy in progressive MS) Degeneration may be reduced by treatment in the RR phase with e.g. B-IFN, alemtuzumab, natalizumab, but not for secondary progressive

Question 54

Risk with use of monoclonal Abs e.g. natalizumab, alemtuzumab

Answer 54

Increased risk of JC virus which causes PML (progressive multifocal leukoencephalopathy)