CORTEX/ SUBCORTICAL DISORDERS
HUNTINGTON DISEASE (HTT 4p16.3)
CHOREA (90%)
PSYCHIATRIC MANIFESTATIONS
PARKINSONISM/ DYSTONIA
ATAXIA/TICS
NO FAMILY HISTORY IN 8%
HDL1 (PRPN)
EARLY TO MID ADULTHOOD
FAMILIAL PRION DISEASE
PHENOTYPES:
GENETIC CREUTZFELDT JACKOB DISEASE
FAMILIAL FATAL INSOMNIA
GERSTMANN STRAUSSLER DISEASE (PRPN MUTATION)
PSYCHIATRIC MANIFESTATIONS
CHOREA/ PARKINSONISM
ATAXIA/ MYOCLONUS
HDL2 (CAG REPEAT >40 JPH3)
EARLY TO MID ADULTHOOD
CLINICALLY SIMILAR TO HUNTINGTON'S DISEASE
PSYCHIATRIC MANIFESTATIONS
DEMENTIA/ ATAXIA
CHOREA/ PARKINSONISM
C9ORF72 (ALS-FTD)
AGE OF ONSET 8-80YRS
PHENOTYPES:
HD/ PSP/ CBS/ MSA/ FTD
PARKINSONISM/ CHOREA
DYSTONIA/ ATAXIA (RARE)
MND/ PLS
30% PRESENT WITH MOVEMENT DISORDER
OTHERS MEAN TIME TO MD 3.5YRS
CREUTZFELDT JACOB SYNDROME
EXTRAPYRAMIDAL/ PYRAMIDAL
CEREBELLAR/ VISUAL
AKINETIC MUTISM
LYSOSOMAL DISORDERS
GAUCHER DISEASE (GBA)
GD1: ADULT GD
VARIED AGE PRESENTATION
COGINITION/ PARKINSONISM
TREMOR/ ATAXIA
INCREASED RISK FOR PD (10x)
POOR RESPONSE TO LEVODOPA
NO EYE MOVEMENT ABNORMALITY
ACUTE PAINFUL BONE CRISIS
NIEMANN PICK C DISEASE
VSGP/ GELASTIC CATAPLEXY
PARKINSONISM
ATAXIA/ DYSTONIA/ CHOREA
HEPATOSPLEENOMEGALY
THROMBOCYTOPENIA
BASAL GANGLIA
NEUROFERRITINOPATHY
ORO-MANDIBULAR DYSKINESIA (85%)
JAW DYSTONIA/ BLEPHAROSPASM
FOCAL LOWER LIMB CHOREA /DYSTONIA
ACUTE BALLISMUS
LIP-SMACKING/ WRITER'S CRAMP
FRONTAL SUBCORTICAL COGNITIVE DYSFUNCTION
ACERULOPLASMINEMIA
AGE OF ONSET 30-70YRS
OROFACIAL DYSTONIA/ CERVICAL DYSTONIA
COGNITIVE DECLINE/ ATAXIA
DIABETES MELLITUS/ LIVER DYSFUNCTION
RETINAL DEGENERATION
LAB: ABSENT CERULOPLASMIN
HETEROZYGOUS: MODERATELY REDUCED LEVEL
INCREASED FERRITIN
RX: DEFERIPRONE STARTING DOSE 15MG/KG/DAY
TWO DIVIDED DOSES
CAN TITRATE TO MAX 50MG/KG/DAY
PHLEBOTOMY 300ML EVERY 15 DAYS
FAHR SYNDROME
NEUROPSYCHIATRIC/ SEIZURES/ HEADACHE
PARKINSONISM/ DYSTONIA/ CHOREA
ATAXIA/ TREMOR
SLC20A2
COGNITION/ HEADACHE/ SEIZURES
PARKINSONISM
PDGFB
COGNITION/ HEADACHE/ SEIZURES
PARKINSONISM/ ATAXIA/ CHOREA
PDGFRB
COGNITION/ HEADACHE/ SEIZURES
PARKINSONISM
XPR1
COGNITION/ HEADACHE
PARKINSONISM/ ATAXIA
MYORG
COGNITION/ PARKINSONISM/ ATAXIA
JAM2
COGNITION/ PARKINSONISM/ ATAXIA/ DYSTONIA
MRI: CALCIFICATION
BG/ THALAMUS/ CEREBELLUM/ WM
MYORG: CENTRAL PONS CALCIFICATION
CEREBELLUM/ CEREBELLAR AFFERENTS
SPINOCEREBELLAR DISORDERS
SCA2,3,6 AND 17 CAN HAVE VERY LATE AGE ONSET (> 70)
COGNITION
SCA8 (ATXN8 CAG REPEAT)
ATAXIA/ SPASTICITY
PSYCHIATRIC SYMPTOMS/ COGNITIVE DECLINE
SCA10 (ATXN10 CAG REPEAT)
ATAXIA/ EPILEPSY
SCA13 (KCNC3 MISSENSE MUTATIONS)
ATAXIA
INTELLECTUAL DISABILITY
SCA 17 (TBP CAG REPEAT)
PSYCHIATRIC SYMPTOMS/ DEMENTIA
ATAXIA/ SPASTICITY/ CHOREA
PARKINSONISM
AUTONOMIC DYSFUNCTION
SUPRANUCLEAR GAZE PALSY
PHENOTYPE
PSP/ MSA/ HUNTINGTON'S DISEASE
SCA19/ SCA22 (KCND3 MUTATION/ DELETION)
COGNITION AFFECTED
MYOCLONUS
SCA48/ SCAR16 (STUB1)
ATAXIA/ COGNITION
EXECUTIVE DYSFUNCTION
PSYCHIATRIC SYMPTOMS
HYPOGONADISM
OPHTHALMOPARESIS
DYSTONIA/ SPASTICITY/ CHOREA
MRI: DENTATE HYPERINTENSITY (T2)
CRAB SIGN
POSTERIOR VERMIS ATROPHY
PARKINSONISM
SCA3 (ATXN3 CAG)
ATAXIA/ PARKINSONISM/DYSTONIA
CPEO/ BULGING EYES
SPASTICITY/ AMYOTROPHY
FACIAL LINGUAL ACTION INDUCED FASCICULATIONS
SCA8 (ATXN8OS, CTA/ CTG REPEATS)
SMALL REPEATS/ EARLY ONSET
PARKINSONISM
LARGE REPEATS/ LATE ONSET
ATAXIA
PHENOTYPE
PSP/ CBS
SCA 17 (TBP CAG REPEAT)
PSYCHIATRIC SYMPTOMS/ DEMENTIA
ATAXIA/ SPASTICITY/ CHOREA
PARKINSONISM
CHOREA
SCA 17 (TBP CAG REPEAT)
PSYCHIATRIC SYMPTOMS/ DEMENTIA
ATAXIA/ SPASTICITY/ CHOREA
PARKINSONISM
AUTONOMIC DYSFUNCTION
SUPRANUCLEAR GAZE PALSY
PHENOTYPE
PSP/ MSA/ HUNTINGTON'S DISEASE
SCA48/ SCAR16 (STUB1)
ATAXIA/ COGNITION
EXECUTIVE DYSFUNCTION
PSYCHIATRIC SYMPTOMS
HYPOGONADISM
OPHTHALMOPARESIS
DYSTONIA/ SPASTICITY/ CHOREA
MRI: DENTATE HYPERINTENSITY (T2)
CRAB SIGN
POSTERIOR VERMIS ATROPHY
MYOCLONUS
SCA14 (PRKCG MISSENSE MUTATIONS)
ATAXIA/ MYOCLONUS
ATAXIA (PURE)
SCA5 (SPTBN2 DELETION/ MISSENSE)
ATAXIA
SCA6 (CACNA1A CAG REPEAT)
DOWNBEAT NYSTAGMUS
PURE CEREBELLAR ATAXIA
SCA15/ SCA16 (KCND3 MISSENSE MUTATIONS)
ATAXIA
SCA31 (BEAN1 INTRONIC TGGAA REPEAT)
ATAXIA
OCULAR SIGNS
SCA1 (ATXN2 CAG)
OPHTHALMOPLEGIA
SPASTICITY/ SENSORY NEUROPATHY
SCA2 (ATXN2 CAG)
OPHTHALMOPLEGIA
SLOW SACCADES
SENSORY NEUROPATHY
SCA3 (ATXN3 CAG)
OPHTHALMOPLEGIA/ BULGING EYES
PARKINSONISM
SPASTICITY/ AMYOTROPHY
SCA6 (CACNA1A CAG REPEAT)
DOWNBEAT NYSTAGMUS
PURE CEREBELLAR ATAXIA
SCA7 (ATXN7 CAG)
VISION LOSS
OPHTHALMOPLEGIA
SPASTICITY
SCA28 (AFG3L2 MISSENSE MUTATIONS)
OPHTHALMOPLEGIA/ PTOSIS
ATAXIA/ SPASTICITY
SCA37 (DAB1 INTRONIC ATTTC REPEAT)
ATAXIA
ABNORMAL VERTICAL EYE MOVEMENT
NEUROPATHY/ AMYOTROPHY
SCA1 (ATXN2 CAG)
OPHTHALMOPLEGIA
SPASTICITY/ SENSORY NEUROPATHY
SCA2 (ATXN2 CAG)
OPHTHALMOPLEGIA
SLOW SACCADES
SENSORY NEUROPATHY
SCA3 (ATXN3 CAG)
OPHTHALMOPLEGIA/ BULGING EYES
PARKINSONISM
SPASTICITY/ AMYOTROPHY
SCA36 (NOP56 INTRONIC GGCCTG REPEAT)
ATAXIA/ AMYOTROPHY
HEARING LOSS
AUTOIMMMUNE
GAD AB
PHENOTYPE:
ATAXIA/ PARKINSONISM/ PSP
STIFF PERSON SYNDROME
STARTLE MYOCLONUS
OPSOCLONUS-MYOCLONUS
ORTHOSTATIC TREMOR
LIMBIC ENCEPHALITIS/ MTLE
ABNORMAL SACCADES
VELOCITY/LATENCY/ACCURACY
SACCADE INITIATION/ EARLY UPGAZE PALSY
NYSTAGMUS
DOWN/ UP BEAT NYSTAGMUS
PERIODIC ALTERNATING NYSTAGMUS
FLUTTER/OPSOCLONUS/ STIFF EYES
>50YRS: 8%+VE GAD POSITIVE
CASPR2 AB
EPISODIC ATAXIA
NEUROMYOTONIA/ MYOKYMIA
CRMP5/ CV2 AB
PARKINSONISM/ ATAXIA/ CHOREA
AUTONOMIC DYSFUNCTION
MSP-P PHENOTYPE
BILATERAL OPTIC NEUROPATHY
SMALL CELL CARCINOMA LUNG
MRI: BASAL GANGLIA HYPERINTENSITY
PERIVENTRICULAR/ INTERNAL CAPSULE HYPERINTENSITY
AMPHIPHYSIN AB
NEUROPATHY/ ENCEPHALOPATHY
MYELOPATHY/STIFF PERSON SYNDROME
CEREBELLAR ATAXIA
NEOPLASIA: SMALL CELL LUNG CARCINOMA
GFAP AB
MENINGO-ENCEPHALO-MYELITIS
ATAXIA (30%)
TREMORS(30%)
PSYCHIATRIC(30%)
AUTONOMIC (30%)
DPPX6 AB
THORACIC STIFFNESS
BRAIN STEM INVOLVEMENT
GI DYSAUTONOMIA
DIARRHOEA/CONSTIPATION
WEIGHT LOSS
IgLON5 AB
SLEEP PROBLEMS:
OSA/RBD/NREM/ STRIDOR
OCULAR:
SACCADIC INTRUSIONS/ VSGP
SYMPTOMS:
COGNITION/SEIZURES/ENCEPHALOPATHY
PARKINSONISM/DYSTONIA/ATAXIA
OROMANDIBULAR DYSTONIA
OROFACIAL DYSKINESIA
HYPEREKPLEXIA
MYORHYTHMIA/ TREMOR
AUTONOMIC DYSFUNCTION
DIABETES INSIPIDUS/ MYOKYMIA
PHENOTYPES
CBS/ PSP/MSA/HD/SPS/MND
RI AB
AGE OF ONSET >40YRS
SUBACUTE ONSET PARKINSONISM
JAW CLOSING DYSTONIA
PSP PHENOTYPE
OCULOPALATAL-MYOCLONUS
NEOPLASIA: BREAST/ OVARY
YO AB
BREAST/ OVARY
HU AB
SMALL CELL LUNG CARCINOMA
TR/mGLuR1 AB
HODGKIN LYMPHOMA
VGCC AB
LAMBERT EATON SYNDROME
ZIC4 AB
SMALL CELL LUNG CARCINOMA
PCA2 (MAP-1B IgG )
ATAXIA/ COGNITION/ NEUROPATHY
SCLC 80%
TPO AB
STROKE/ ENCEPHALOPATHY
CSF ABNORMAL 80%
PROTEIN INCREASED
GQ1b AB
CANOMAD
CHRONIC ATAXIA NEUROPATHY, OPHTHALMOPLEGIA, IGM PARAPROTEINAEMIA
COLD AGGLUTININS
MILLER FISCHER SYNDROME
ATAXIA/OPHTHALMOPARESIS
BICKERSTAFF ENCEPHALITIS
SPASTICITY/UPGOING PLANTERS
GALOP SYNDROME
GAIT ATAXIA LATE ONSET POLYNEUROPATHY
LAB: M-BAND IGM
NEUROCHONDRIN IgG AB
MCP AND PONS HYPERINTENSITY
SEPTIN-5 AB
OSCILLOPSIA/ VERTIGO
METABOLIC/ SPORADIC
VIT B1 DEFICIENCY (WERNICKE)
CONFUSION/ OPHTHALMOPARESIS
GAZE EVOKED/ UPBEAT NYSTAGMUS
PERIPHERAL NEUROPATHY
HYPOPHOSPHATEMIA
WERNICKE MIMIC
HYPOMAGNESEMIA
ATAXIA/ UPBEAT NYSTAGMUS
VIT B6/VIT B12/ VIT E DEFICIENCY
HYPOTHYROIDISM
SUPERFICIAL HEMOSIDEROSIS
SYPHILIS
DEMENTIA/ PSYCHIATRIC MANIFESTATIONS
MYELOPATHY (TABES DORSALIS)
ARGYLL ROBERTSON PUPIL:
SMALL PUPILS/ NO DILATION IN DARK
NO REACTION TO LIGHT/ CONSTRICT WHEN FOCUSED
RARE: PURE CEREBELLAR ATAXIA
DIAGNOSIS:
CSF: VDRL (INSENSITIVE)
CSF: TREPONEMAL ANTIBODY/ TPHA (HIGH SENSITIVE)
WHIPPLE'S DISEASE
OCULOMASTICATORY SKELETAL MYORHYTHMIA
DEMENTIA/ SUPRANUCLEAR OPHTHALMOPLEGIA
MENINGITIS/ CONFUSION/ HEADACHES
PSP PHENOTYPE: PARKINSONISM, UPGAZE RESTRICTION
VERTICAL SACCADE SLOWING
CONVERGENT DIVERGENT NYSTAGMUS (1HZ)
MYOCLONUS/ CHOREA/ MYORHYTHMIA (40%)
ATAXIA (10%)
ARTHRALGIA/ DIARRHOEA/ WEIGHT LOSS
LYMPHADENOPATHY
CAN PRESENT WITHOUT GI SYMPTOMS
DIAGNOSIS:
DUODENAL BIOPSY
CSF: PAS MACROPHAGES/ NORMAL CYTOLOGY(60%)
TROPHERYMA WHIPPLEI PCR: CSF/ BIOPSY
MRI:
FOCAL/ MULTIFOCAL WM LESIONS IN MES TEMPORAL LOBE/ THALAMUS/ HYPOTHALAMUS/ MIDBRAIN
PERIVENTRICULAR WMH/ PACHYMENINGITIS (10%)
CEREBRAL ATROPHY
RX:
TMP-SMX, DOXYCYCLINE/ 3RD GEN CEPHALOSPORINS
TOLUENE TOXICITY
HEPATOCEREBRAL SYNDROME
ATAXIA/ PARKINSONISM
MRI: GPI HYPERINTENSITY (T1)
MCP HYPERINTENSITY (T2)
CELIAC DISEASE
ATAXIA/ LEG MYOCLONUS
NEUROPATHY/ DIARRHOEA
GOBBI SYNDROME: CEC SYNDROME
CELIAC DISEASE/ SEIZURES/ BILATERAL
MRI: OCCIPITAL CALCIFICATIONS
LAB: ANTI-TTG ANTIBODIES