Worsening Weakness and Numbness Flashcards
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?
Location of numbness (including sensory level)
Course
Onset
Duration
Other symptoms (e.g. visual disturbance, bowel and bladder symptoms including frequency, urgency and incontinence)
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?
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
How can Sjogren’s syndrome affect the CNS?
Can produce inflammatory change in spinal cord
What paraneoplastic syndromes can affect the CNS?
Paraneoplastic cerebellar degeneration (typically in small cell lung cancer), causing ataxia
Peripheral neuropathy (chronic sensorimotor neuropathy)
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?
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
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
Paraparesis with sensory level
Heat sensitive symptoms
Uhthoff’s phenomenon
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
Lhermitte’s sign
Electrical sensation that runs down the back and into the limbs, elicited by bending the head forward
Describe a simplified approach to determining the anatomical cause of sensory loss
Describe a simplified approach for localisation of the cause of neurological symptoms
What are 3 clinical features suggestive of a spinal cord pathology over a peripheral neuropathy?
Sensory level
Hyperreflexia
Bowel and bladder problems
What are 2 clinical features suggestive of a peripheral neuropathy over a spinal cord pathology?
Glove and stocking, dermatomal or single nerve distribution
Loss of reflexes
DDx for subacute paraparesis
Spinal cord pathology: MS, tumour
Peripheral nerve lesions: GBS (acute demyelinating polyradiculopathy)
What features of Helen’s case are not consistent with GBS as an underlying cause?
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
DDx for acute paraparesis
Trauma
Spinal cord stroke or SAH (usually in people with advanced arteriopathy)
What is the cardinal feature of spinal cord stroke?
Rapid weakness but preservation of dorsal column function, because stroke almost always involves the anterior spinal supply
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
UMN signs with a sensory level confirming this is in the spinal cord above or at T4
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?
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)
Neuromyelitis optica
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
What does Helen’s MRI show?
Ovoid inflammatory lesion in the cervical cord (“plaque”)
Confirms the Dx of a partial transverse myelitis
What is inflammatory myelitis?
Inflammatory demyelination of segment(s) of spinal cord
Functionally transects the cord
Causes of transverse myelitis
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)
Possible complication of VZV infection in immunosuppressed patients
Necrotising myelitis (in association with shingles)
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?
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)
What are the 4 most common first presentations of MS?
Transverse myelitis
Optic neuritis
Brainstem/cerebellar presentations (ataxia, nystagmus, vertigo, diplopia)
Incidental or with fatigue/non-specific Sx (nowadays more common)
How is MS diagnosed?
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
DDx for MS
Neuromyelitis optica (NMO, Devic’s disease)
Other systemic AI diseases
Acute disseminated encephalomyelitis (ADEM)
Sarcoidosis
Infections (e.g. brain abscess)
Tumours
Conversion disorder, somatisation
Acute disseminated encephalomyelitis
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
Causative organisms for brain abscess
GAS
Nocardia
What is the most common presentation of systemic sarcoidosis?
Pulmonary involvement (SOB, cough, fatigue)
Characteristic appearance of sarcoidosis on XR
Bilateral hilar lymphadenopathy (bilateral enlargement of LNs of pulmonary hila); describes the enlargement of mediastinal LNs and is most commonly identified by a CXR
What is a cold abscess?
A patient with a cold abscess does not appear systemically unwell
What factors are predictive for a second attack of MS?
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
What is MS? Describes its epidemiology, pathogenesis, presentation and natural Hx
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
Describe the 3 main subtypes of MS
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
What factors are suggestive of a better prognosis in MS?
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
Describe the natural Hx of MS
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
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?
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)
How is MS relapse defined? What is the prognosis of a relapse?
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
Mx of MS relapse
Why can’t an oral at-home option be used?
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)
SEs of IV methylprednisolone
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)
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?
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
List disease modifying therapies currently available for the treatment of MS
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)
Common presentations of MS relapses (in descending order of incidence)
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)
What is pyramidal weakness?
Predominantly flexion weakness in LL (hip flexion, knee flexion, ankle dorsiflexion) or extension weakness in UL
Common permanent MS symptoms
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)
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?
Start symptomatic therapy with SSRI (e.g. escitalopram 10mg daily) OR commence psychotherapy (insufficient evidence to support combination therapy of depression)
Possible social consequence to consider in a young person with chronic illness
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
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?
Neurology
Rehab physicians
Continence/urology
Pain
Psychology
Patient support groups (MS society)
What kinds of supports does formal rehab provide?
Symptomatic and supportive therapies: multidisciplinary involvement (medical, nursing, PT, OT, ST, psychology, SW)
May be inpatient or outpatient/community-based
Problem-solving education process
What are the goals of rehab in MS?
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)
How can fatigue be managed in MS?
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
Helen retires early (40-50s) due to deterioration in gait and repeated falls (experiences weakness, spasticity, ataxia/incoordination, imbalance, fatigue)
Dx? Mx?
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
Risk with use of monoclonal Abs e.g. natalizumab, alemtuzumab
Increased risk of JC virus which causes PML (progressive multifocal leukoencephalopathy)
