neurodegenerative and neuromuscular disorders Flashcards
weakness
-Weakness is one of the presenting symptoms for the topics in this lecture
-Vague chief complaint
-Incorrect diagnosis of generalized weakness as high as 50% in ED
-Historical questions should assess:
-Fatigue or true weakness (neuromuscular)?
-Associated symptoms? Fever, exposures, prodromal illness, level of consciousness, sensory abnormalities, cortical findings (aphasia, hemineglect, agnosia, gaze preference, visual deficit), muscle cramping, bowel or bladder sxs.
-PMH: Lifestyle/med changes, psychiatric conditions, comorbidities
-Distribution of weakness? Bilateral vs unilateral. Upper vs lower. Monoradicular. Myotomal. Ocular (diplopia, ptosis), bulbar (voice change).
-Pattern? Proximal vs distal. Fluctuating weakness.
-Duration of weakness?
-Acute (seconds to minutes): CVA, ICH, hypoglycemia, poisoning, spinal cord syndromes, periodic paralysis.
-Subacute (hours to days):Botulism, tetanus, Myasthenia gravis crisis, GBS, transverse myelitis, electrolytes (hypokalemia, hyponatremia), conversion disorder
-Chronic (weeks to months):Amyotrophic lateral sclerosis, psychiatric disorders (e.g. depression)
motor pathway (a review)
-CORTICOSPINAL TRACT (PRYRAMIDAL TRACT)
-Upper motor neuroncell bodies lie in themotor cortex(within the precentral gyrus).
-Their axons travel in the subcortical white matter within the posterior limb of the internal capsule.
-They run through the cerebral peduncles into the ventral/anterior brainstem.
-They cross (decussate) at the junction of the medulla and the cervical spinal cord.
-They run down the posterolateral spinal cord.
-Finally, upper motor neuron axons synapse ontolower motor nerveswithin the anterior horn of the spinal cord grey matter
-CORTICOBULBAR TRACT
-Primarily involved in carrying the motor function of the non-oculomotor cranial nerves (e.g. cranial nerves V, VII, IX, XII, and motor region of cranial nerve X.)
-The corticobulbar tract originates in the primary motor cortex of frontal lobe, just superior to the lateral fissure and rostral to the central sulcus in the precentral gyrus.
-It descends via corona radiata and genue of internal capsule with a few fibers in the posterior limb of internal capsule.
-In the midbrain the internal capsule becomes the cerebral peduncle.
-The corticobulbar fibers exit at the appropriate level of the brainstem to synapse on the lower motor neurons of the cranial nerves ( V, VII, IX, XII, the motor regions of cranial nerve X in the nucleus ambiguus.)
-The corticobulbar tract innervates cranial motor nuclei bilaterally with the exception of the lower facial nuclei (which innervates facial muscles below the eyes) and the genioglossus muscle, which are innervated only unilaterally by the contralateral cortex
localizing weakness
-LMN- peripheral nerves
-pronator drift- stroke
-hoffman sign- when you flick middle finger the pointer and thumb come together
motor weakness
cerebral palsy
-a group of permanent NON PROGRESSIVE neurologic disorders thataffects pts ability to move and maintain balance and posture.
-MC motor disability in children
-injury during development of baby’s brain up to 3 years of age
-1.5 to 2.5 per 1000 live births - quite common
-Usually dx in first 2 years of life
-Symptomatology varies person to person
-There is NO cure, but there IS tx
-Several co-morbidities: epilepsy (35-50%), intellectual disability (30-50%), feeding difficulties, visual abnormalities, hearing abnormalities, communication difficulties
-a motor problem! -> dont assume intellectual disability
cerebral palsy risk factors
-IDIOPATHIC
-Prenatal:
-Prematurity is MC!
-Low birth weight!
-Multiple gestations
-Intrauterine growth restrictions (IUGR)
-Maternal substance abuse
-Congenital brain malformations
-Intrauterine infections (TORCH)
-Intrauterine stroke
-Chromosomal abnormalities
-Radiation exposure
-perinatal:
-Hypoxic-ischemic insults
-Central nervous system (CNS) infections
-Stroke
-Kernicterus- high bilirubin
-postnatal:
-Accidental and non-accidental trauma
-CNS infections
-Stroke
-Anoxic insults
cerebral palsy hx and PE
-History:
-Birth and prenatal history
-Slow reaching of development milestones
-Delayed MOTOR development (not regression)
-Poor feeding, poor sleeping
-Difficult to handle / cuddle
-Possible seizures or epilepsy
-Physical exam:
-Micro or macro-cephaly
-Excessive irritability or diminished interaction
-Hyper or hypo- tonia (poor head control, back arching)
-Muscle weakness, spasticity, dystonia (inability to sit up at 8 months, abnormal posture)
-Persistent primitive reflexes
-if baby is only using one hand (they normally dont have preference) -> it may suggest the other hand is weak
cerebral palsy classification
-Spastic types are MC!
-Spastic ~75%
-Affected area: Brain cortex UMNs
-Movements are stiff and jerky
-!!Scissor gait or toe walking
-↑ Tone, ↑ DTRs, +Babinski
-Non-spastic types involve abnormal involuntary movements that worsen with stress and stop with sleep
-Dyskinetic ~20%:
-Affected area: Central brain esp BASAL GANGLIA
-Excessive involuntary movements leading to poor coordination and body posture
-can be assoc with Kernicterus- high bilirubin
-Ataxic ~5%:
-Affected area: Cerebellum
-Balance problems, incoordination, intention tremors, hypotonia
-trouble sitting up right, hand to nose test failure
-Mixed
cerebral palsy clinical dx
-!Serial examinations! of motor development
-Infectious Work-up (ToRCHS titers)
-Metabolic or genetic testing may be considered
-EEG – if seizures suspected
-Screen for: ID, ophthalmologic abnormalities, hearing/speech/language impairment, growth failure
-Diagnostic imaging to detect causative lesions
-MRI brain- to r/o other stuff
-Cranial ultrasounds: intracerebral hemorrhage, structural abnormalities, hypoxic/ischemic injuries -> fontanelles arnt closed yet
-Specify subtype after 18-24 mo
-toxo is MC- cats
-coxakie
-syphilis is up and coming
-
cerebral palsy management
-Management -> maximizing pt independence and treating symptoms
-Durable medical Equipment: motorized wheelchairs, communication systems, voice-activated computers, etc.
-Treatment of spasticity, dystonia, other orthopedic issues
-OT/PT, orthotics, standers, braces, seating systems, medications, etc.
-Generalized spasticity: PO Baclofen or Benzos (First line)
-Localized spasticity: Botulinum neurotoxin (BoNT) injections
-Pain control
-Sleeping modalities
-Management of seizures (if present)
-Vision and/or hearing impairment treatments
-Speech/language therapy
-Regular feeding/nutritional status assessments, monitor growth
-Treat GI symptoms (dysmotility, constipation, GERD), respiratory problems (recurrent aspiration, lung disease, OSA,laryngomalacia), sialorrhea
-Preventive measures to prevent skin breakdown/ulcers – repositioning, pressure support devices, skin care
-Manage urinary function, sleep problems, and recognize and treat pain
34 year old female with no PMH
C/O L eye blurry vision and diplopia
On history, she also reports intermittent episodes of numbness and weakness that occur from her chest downwards, these began several years ago. Each episode lasted a few weeks.
Your motor and sensory exam is normal,
Your eye exam is abnormal showing internuclear ophthalmoplegia (see video)
With these intermittent neurologic symptoms and ocular findings, what is the likely diagnosis, and what is your next step in evaluation?
-cant actively adduct the eye
-UPN
multiple sclerosis
-Autoimmune!, inflammatory! disease that causes !demyelination! of the CNS! (oligodendrocytes), with degeneration of !white and gray! matter of the !brain, optic nerves, and spinal cord!
-affects the UMN
-sends distorted messages
-Etiology is unknown
-Genetic predisposition: HLA-DRB1*15
-Environmental risk factors: Low vit D, cigarette smoking
-Caucasians and black population
-!!Young adults 20-40yo
-Female > Male (3:1)
-Severe disability within 20-25 years in half 25% of patients
-shortens life span by about 7 years
MS pathophysiology
-Pathophysiology not completely understood
-Autoimmune inflammation, demyelination, axonal degeneration
-Common theory: Activation of T-lymphocytes -> inflammatory process -> focal demyelination with preservation of axons (plaques/scarring) -> loss of axons and atrophy of oligodendrocytes (chronic plaques) -> gliosis -> inadequate remyelination
-we see plaques and scars on MRI
-symptoms come and go and keep getting worse
-Definitions:
-!!MS exacerbation aka attack, relapse, flare: New or significant worsening symptoms of CNS demyelination ≥24 hrs
-Remission: Period of recovery after exacerbation in which clinical sxs resolve or mostly resolve
-Pseudorelapse: Recurrence or significant worsening due to stressors (infection, heat)
MS classifcations
-MC- relapsing-remitting- episodic exacerbations - 80-90%
-with time the damage builds up
-secondary progressive- relapse remitting that becomes progressive- 50%
-you had relapsing-remitting, now there is constant inflammation with flares
-primary progressive disease- decline without acute exacerbations- 10%
-no exacerbations but keeps getting worse
MS clinical features
-Symptoms last > 24 hours duration
-Frequency of episodes ~ 1 per year
-!!Fatigue (85%), headache
-Optic neuritis! is a classic finding- MC and specific
-Internuclear ophthalmoplegia [INO]
-Diplopia with lateral gaze due to weak medial rectus (but intact convergence)
-Due to lesion of the medial longitudinal fasciculus (MLF)
-Understand INO here: youtube video here
-didnt go over this much
-Cerebellar involvement: poor postural control (ataxia), imbalance, gait dysfunction, scanning speech, nystagmus, intention tremors, pronator drift
-Demyelination of spinal cord tracts symptoms
-Cranial nerve palsies
-!Trigeminal neuralgia (unilateral > bilateral)
-Diplopia, facial palsies
-Autonomic dysfunction- Bladder, bowel incontinence or sexual dysfunction (impotence)
-!UTHOFFs phenomenon: symptoms worsen in heat
MS: demyelination of spinal cord tracts
-LHERMITTEs sign: neck flexion causes lightning shock-like pain down the spine
-UMN: weakness, hyperreflexia, spasticity, Babinski
-Dorsal spinal column: loss of vibration and fine touch sensation, numbness, paresthesia’s, ataxia
-Neuropathic pain: Numbness, paresthesia’s, proprioception, temperature changes
MS optic neuritis
-Optic neuritis! is a classic finding- MC and specific
-1st sign in up to 30% of MS
-Unilateral eye pain
-Worse with eye movements
-optic nerve is SENSORY
-Monocular vision loss and color blindness (esp RED)- dull colors
-Relative afferent pupillary defect (RAPD) aka Marcus gunn pupil – Delayed conduction of a swinging light to affected optic nerve causing pupil dilation -> she said just know these things exist
Other differentials for optic neuritis include:
-Infection (lyme, herpes, syphilis)
-Autoimmune disorders (SLE, Sarcoid)
-Methanol poisoning
-B12 deficiency
-Diabetes
MS dx criteria
-Clinical diagnosis of exclusion. Episodes must be separated by “time and space”:
-≥ 1 objective and unprovoked clinical episode lasting >24h
-Time: 2nd clinical episode or new lesion on follow up MRI
-Space: Multifocal symptoms or multiple CNS lesions on MRI
-Exclude mimics
-McDonald Criteria on MDCALC (dont need to know)
MS testing
-!!MRI brain ± spinal cord w/ gadolinium: test of choice
-!!!Multiple sclerotic plaques (T2 hyper densities)
-MC found in periventricular white matter
-Can have !dawson fingers!, finger-like radial extensions
-contrast enhanced active lesions often resolve after 2-8 weeks
-Additional studies for differentials
-CSF analysis:
-↑ IgG (oligoclonal bands) – nonspecific, inflammatory
-Exclude infectious pathology
-Visual evoked potentials -Slowed optic nerve conduction
-Lab studies:
-CBC, B12, TSH, ANA, Lyme, RPR (syphilis), HIV, MMA
-picture shows dawson fingers
C4 level demyelinating plaque
amyotrophic lateral sclerosis
-both UPPER and LOWER motor neurons
-AKA Lou Gehrig’s disease
-!!Neurodegenerative disease of BOTH upper AND lower motor neurons!
-Entirely motor
-Gradually lose the ability to initiate and control voluntary movements
-eventually affects breathing
-Exact pathophysiology is unknown
-Smoking is a risk factor
-Insidious and progressive
-Will lead to eventual paralysis and death
-!!Most will die within 3-5 years from onset of symptoms
-No cure
ALS PE
-Generalized limb weakness (more than truncal) with gait abnormalities
-UMN symptoms (70-80%):
-!Weakness, hyperreflexia, spasticity,Primitive reflexes (esp Babinski), hypertonia, Clasp knife reflex, pronator drift
-LMN symptoms (70-80%):
-Weakness, atrophy (reduced muscle bulk and tone),fasciculations, hypotonia, hyporeflexia
-Cranial nerves (10-20%):
-Dysarthria, Hoarseness of voice (CN X), Dysphagia/choking (CN X,XII)
-Pseudobulbar affect: Inappropriate and involuntary crying, laughing
-!Bowel and bladder and extraocular muscles* tend to be conserved (unlike MG…)
-Late signs: muscle atrophy, hyporeflexia, babinski positive, spasticity, weight loss, choking, respiratory failure
A 39-year-old female with no significant medical history presents with complaint of weakness. Symptoms have been present for the past three weeks. She describes difficulty climbing stairs and frequently has to take breaks before continuing. She reports that over the past 24 hours, she has been experiencing double vision when watching television and difficulty chewing.
Vital signs: T 98.8°F, HR 72, BP 136/78, RR 22, O2sat 97% on room air.
Physical Exam: The patient appears fatigued but is not in any distress. Breath sounds slightly diminished but otherwise clear. Upper and lower extremity strength is 3/5 bilaterally and weakness seems to worsen as the exam continues. Reflexes and sensation are normal. She has left eye ptosis and a deconjugate gaze.
myasthenia gravis
-proximal weakness- stair require quads
-3 weeks is a long time
-fatigue
-weak and worsens with exam
MG signs and symptoms
-!!Ocular involvement is the most common initial symptom
-Ptosis more noticeable with upward gaze!!!!!!!!!!!!!!!!!!
-Diplopia due to extraocular muscle weakness
-No pupil involvement, can be unilateral > bilateral
-!!Fluctuating asymmetric muscle weakness over the first few years worsens with use, improves with rest!!
-by the end of the day there is weakness
-Proximal muscle weakness > distal!
-Arms > Legs!
-Head drop!
-Generalized type:
-Ocular (above), bulbar (dysarthria, dysphagia, jaw weakness, hypophonia), facial, limb, respiratory
-No sensation or reflex involvement (severe weakness can cause ↓ DTR in late stages)
MG evaluation: imaging and labs
-CT to evaluate for thymus abnormality
-Labs showing
-!!+ Acetylcholine receptor antibodies (anti-AChR) specific
-!!!+ Muscle specific receptor tyrosine kinase antibodies (anti-MuSK)
-test
MG dx
-Edrophonium (Tensilon) test:
-Edrophonium = Acetylcholinesterase inhibitor with rapid onset, short acting
-Prolongs Ach Prescence in the NMJ causing marked improvement
-Can improve weakness in other diseases… ALS, poliomyelitis etc. so it was discontinued by the FDA
-SE- SLUGE
-Ice pack test
-Place ice on eyelid with ptosis for 2-5 minutes and see improvement
-Routine EMG usually normal
-Single fiber EMG will show “jitter” and is more sensitive
-Repetitive nerve stimulation (RNS) shows decreased amplitude with repeated stimulations
LEMS dx and tx
-DDX: Inflammatory muscle diseases such as polymyositis, dermatomyositis
-Diagnosis
-Anti-VGCC antibodies
-Electrodiagnostic testing (NCS, EMG)
-Chest CT to look for SCLC
-Treatment
-If SCLC -> treat the malignancy
-If no cancer:
-Steroids
-Pyridostigmine- ↑ Ach availability
-IV immunoglobulin therapy– Binds and neutralizes the auto antibodies
-Plasmapheresis
botulism diff dx
-Diff dx: Other causes of descending weakness plus cranial nerve palsies:
-Organophosphate intoxication *.
-Presents with manifestations of cholinergic excess. The dominant clinical features include bradycardia, miosis, lacrimation, salivation, bronchorrhea, bronchospasm, urination, emesis, diarrhea, diaphoresis, and generalized weakness.
-Guillain-Barre syndrome (especially the Miller Fisher variant).
-Diphtheria infection.
-!!!Myasthenia gravis (diplopia and ptosis are common)- botulism is continuously progressive
-Tick paralysis- Afebrile ascending flaccid weakness, paralysis and ataxia, without sensory involvement, When the bulbar nerves and diaphragm become involved, respiratory failure ensues.
-Pontine infarction.
-Diagnosis: The diagnosis of botulism is made based on clinical findings and exclusion of other processes
overview chart
major causes of myopathy
