Neurodegenerative disease Flashcards
A 28 year old Norwegian woman presents to A&E after she was unable to fell the hot water on her left leg whilst taking a bath. CSF analysis demonstrated oligoclonal bands that were unmatched with the serum. Which of the following would most likely confirm a diagnosis of Multiple Sclerosis?
A.Multiple lesions on MRI that all enhanced with gadolinium
B.The patient’s symptoms reoccur 1 year later
C.The patient develops blurry vision in one eye a year later
D.The patient reports blurry vision currently
E.A 1 year follow up finds oligoclonal bands matched with the serum
A.Multiple lesions on MRI that all enhanced with gadolinium
B.The patient’s symptoms reoccur 1 year later
C.The patient develops blurry vision in one eye a year later
D.The patient reports blurry vision currently
E.A 1 year follow up finds oligoclonal bands matched with the serum
Multiple sclerosis
Risk Factor:
Cause:
Types:
Diagnosis
Investigations:
Symptoms:
-
Risk factor:
- people living in high latitude - Vit D
- more common in people with autoimmune conditions (psoriasis)
- young white women
- HLA DLRB1*15
- Cause: chronic inflammatory multifocal, demyelinating disease of the central nervous system -> resulting in loss of myelin, and oligodendroglial and axonal pathology
- Types:
- Relapsing and remitting
- Secondary progressive: intial relapsing and remitting and progress to have more relapses superimposed with incomplete recovery
- primary progressive- immidiately progress without relapsing and remitting
-
Diagnosis: clinical Diagnosis (although investigations useful)
- Absence of alternative diagnosis
- Dissemination in time (DIT) (2 different times)
- Dissemination in space (DIS) (2 different places)
-
Investigations:
- Radiological evidence – MRI using gadolinium (GAD) contrast (during inflammation Blood brain barrier becomes leaky allows GAD to cross and light up- shows up for up to 6 weeks)
- Laboratory evidence – CSF - (need oligoclonal bands present in CSF but not in serum- means antibody are only in brain - mean antibodies targeting brain and not just an infection)
- Electrophysiology – VEPs- look for subtle visual abnormalities in viusal pathways - becuase commonly affected by MS
- Symptoms:
- Optic neuritis (visual field defect, diplopia)
- Motor weakness (limb weakness and hyper reflexia)
- Sensory disturbances (paresthesia)
- Urinary urgency & incontinence & sexual dysfuntion
- Fatigue
- Seizure
- Psychiatric distrurbances
- Vertigo and Nystagmus
- Optic neuritis (visual field defect, diplopia)
Myasthenia GRAVIS
Risk Factor:
Cause:
Associations:
Investigations:
Symptoms:
- Risk Factor: young adult women (under 40) and older men (over 60)
- Cause: antibodies block, alter, or destroy the receptors for acetylcholine at the neuromuscular junction (repeated uses increasing amount of ACh to maintain contraction), which prevents the muscle from contracting (can involve MuSK (Muscle-Specific Kinase) protein)
- Association: Thymoma and thymic hyperplasia
-
Investigations:
- Bloods – anti-AChR or anti-MuSK
- EMG
- CT/MRI
-
Symptoms: Fatiguable muscle with normal reflex
- Ptosis
- Diplopia
- •Dysarthria
- •Dysphagia
- •±SOB
Lambert eaton Myesthenic Syndrome
- Cause:
- Associations:
- Investigations:
- Symptoms:
- Cause: antibodies to the calcium channel-> leads to blackage of the calcium channel and no release of acetylcholine -> more movement the more action potential and the more activation of calcium channel -> release of acetylcholine
- Associations: Small cell lung cancer, Autoimmune disease
-
Investigations:
- Bloods – anti-VGCC
- EMG
- CT/MRI
-
Symptoms: weakness where muscles improve with use
- •Difficulty walking
- •Weakness in upper arms and shoulders
- •Similar symptoms to myasthenia gravis
- •Autonomic: Dry mouth, constipation, incontinence
- •Muscles function better following use
- •Hyporeflexia
A 40 year old woman visits her GP complaining of tiredness. On questioning, she reports getting tired when climbing the stairs or during a conversation. She often has to stop what she is doing to regain her energy. The GP asks her to look upwards, and after a few seconds she begins to develop ptosis. What is the most likely diagnosis?
A.Iron Deficiency Anaemia
B.Myasthenia Gravis
C.Lambert Eaton Myasthenic Syndrome
D.Carcinoma
E.Horner’s Syndrome
A.Iron Deficiency Anaemia
B.Myasthenia Gravis
C.Lambert Eaton Myasthenic Syndrome
D.Carcinoma
E.Horner’s Syndrome
A 50 year old man visits his GP complaining of weakness in his right arm. He reports the weakness has gradually developed over the last 2 months. On inspection, the GP notices wasting of his tongue and hyperreflexia. His right arm is rigid. What is the most likely diagnosis?
A.Stroke
B.Multiple Sclerosis
C.Parkinson’s disease
D.Motor Neuron Disease
E.Carpel Tunnel Syndrome
A.Stroke
B.Multiple Sclerosis
C.Parkinson’s disease
D.Motor Neuron Disease
E.Carpel Tunnel Syndrome
Motor neurone disease
- Cause:
- Types:
- Diagnosis:
- Symptoms:
- Signs:
- Investgation:
-
Cause: death of the lateral corticospinal tract -> lack of feeding of muscles
- build of ubiquinated proteins (faulty proteins), killling motor neurons (97% of MND patients have ubiquitin inclusions positive for TDP-43)
-
Types:
- Progressive musclar atrophy: LMN only
- progressive bulbar palsy: Cranial nerves 11-12 (tongue, jaw and voice)
- pseudobulbar palsy: 9-11
- primary lateral sclerosis: upper motor neuron
- Diagnosis: involves upper and lower motor neurones
-
Symptoms:
- Progression muscle weakness
- •Dysphagia
- •Shortness of breath
- •Sparing of oculomotor, sensory and autonomic function (no impairement of bladder, bowel or sexual function)
-
Signs:
- thenar wasting
- bulbar muscle of tongue wasting
-
Investgation:
- EMG- show fasciculations and fibrillations (motor units are polyphasic adn have high amplitude and long conduction)
- BLood: exludes Vit B12, folate deficinecy and other conditions
Parkinsonism
Risk factors:
Cause:
Diagnosis:
Symptoms:
Signs:
Investgation:
-
Risk factors:
- living in the country side - pesticides but evidence is inconclusive
- males more affected 4:1
- Fhx
-
Cause:
- Prakinson disease: loss of dopaminergic neurones due to alpha synnuclein deposition in substantia nigra (need to loose 80% to experience symptoms)
- Drug induced: anti- emetics, anti-psychotics
- Atypical Parkinsonism
- Diagnosis: Clinical diagnosis
-
Symptoms: Triad bradykinesia, rigidity, resting tremor
-
6M’s
- Monotonous, hypotonic speech
- Micrographia
- HypomiMesis (expressionless face)
- March a petit pas - shuffeling gait
- Misery → depression
- Memory loss → dementia
-
6M’s
- Investgation:
What are the types of atypical parkinsonism?
- Multiple system atrophy (Papp- Lantos bodies, early autonomic feature and cerebellar feature)
- Progressive supranuclear palsy- (early postural instability and verticla gaze palsy)
- Corticobasal degeneration- Alien limb Phenomenon
- Vascualar Parkinson’s (legs particularly affected, gait worse than tremor)
- Lewy body dementia - (early dementia + visual hallucination)
What is Parkinson’s dementia?
What are symptoms of it?
Get dementia many years after the onset of Parkinson’s motor symptoms
Symptoms include:
- Amnestic, language deficits
- Visuospatial Dysfunction
- Hallucinations (little people or animals)
- Fluctuations
- Aggression/Anxiety
A 70 year man is referred to a neurologist by his GP. The referral letter notes that the man has slowly been struggling to get around and carry out basic activities like cooking dinner, finding he struggles to initiate movement. The letter also notes that the patient has a resting tremor and rigid upper arms. When the neurologist calls the patient into the room, what gait does he expect the patient to most likely have?
A.Ataxic
B.Hemiplegic
C.Shuffling
D.Scissor
E.Choreiform
A.Ataxic
B.Hemiplegic
C.Shuffling
D.Scissor
E.Choreiform
dementia
- Types:
- Risk factors:
- Cause:
- Symptoms:
- Investgation:
-
Types:
- Alzheimer’s Type Dementia
- Dementia with Lewy Bodies (& PDD)
- Vascular Dementia (CVD)
- Frontotemporal Dementia (FTD)
- Risk factors: increasing age, family history, vascular risk factor, female gender, down syndrome and education
- Cause:
- Beta amyloid plaque formation due to abnormal breakdown product (A-beta) of the amyloid precursor protein with the a and γ secretase
- Tau tangles formation
- Diagnosis:
-
Symptoms: 5A’s
- Amnesia- poor day to day memory, repetitive, get lost
- Anomia
- Apraxia- problems dressing, preparing meals, manual tasks
- Agnosia
- Aphasia
- problems with calculations and attention
-
Investgation: Clinical diagnosis
- MRI - atrophy of medial temporal lobes (hippocampus- memory), cortical atrophy (congnitive symptoms)
- CSF: tau & beta amyloid
- Imaging: CT, MRI, PET, SPECT
- MMSE or MOCA can be used
What is chronic traumatic encephalopathy?
explain the thought mechanism behind it?
have demtia like symptoms
30% of HI patients have Aß deposits -> known to lead to chronic inflammation as well as increases in amyloid levels
Several studies suggest that TBI in early/mid-life is assoc with dementia in later life
Vascular dementia
Cause:
Risk factors
Symptoms:
Investigations:
- Cause: where neuronal death is due to infarction, essentially strokes , but damaging the small and medium sized vessels
-
Risk factors:
- ♂>♀
- Elderly
- CVD risk factors
-
Symptoms: Sudden onset, Stepwise deterioration
- Like AD
- Location-specific deficits
- Emotional and personality changes
- Focal neurology
-
Investigations:
- MRI shows hemosiderin deposits from previous infarcts
Fronto temporal dementia- Pick’s disease
- Cause:
- Risk factors
- Symptoms:
- Cause: Pick’s bodies - Hyperphosphyorlated tau protein (doesn’t involve amyloid beta), only affects the frontal and temporal lobes
- Risk factors: 40-60 years old, FHx,
-
Symptoms:
- Personality change
- Disinhibition
- Overeating, preference for sweet foods
- Emotional blunting
- Relative preservation of memory
- -> Causes death within 5-10 years
