ATAXIA
TARGETED TREATMENT
CEREBROTENDINOSUS XANTHOMATOSUS
CHENODEOXYCHOLIC ACID
5-15mg / kg total daily dose in 3 divided doses
Maximum dose = 1000mg/day
​
MULTIPLE SYSTEM ATROPHY
AMANTADINE​
Maximum dose 300mg/ day in 3 divided doses
​
SCA38 (ELOVL5)
DOCOSAHEXAENOIC ACID
600mg /day
​
FRIEDREICH ATAXIA
COENZYME Q10
400mg/day
​
VIT-E (TOCOPHEROL)
800mg/day
​
IDEBENONE (SIMILAR TO COENZYME Q10)
20 mg/kg/day
​
REFSUM (PHYN/PEX7)
AVOID PHYTANIC ACID
HIGH CALORIC DIET: PREVENT MOBILIZATION OF PHYTANIC ACID FOR ADIPOSE TISSUE
​
VITAMIN RESPONSIVE DISORDERS
BIOTINIDASE DEFICIENCY
BIOTIN 5MG BID
​
MULTIPLE CARBOXYLASE DEFICIENCY
BIOTIN 5 MG BID
​
MTHFR MUTATION
PYRIDOXINE/ TETRAHYDROFOLATE
​
COBALAMIN C DEF (CB1C)
VITAMIN B12/ CARNITINE/ FOLIC ACID
RIBOFLAVIN TRANSPORTER DEFICIENCY
RIBOFLAVIN 10 MG BID
​
EPISODIC ATAXIA
EA1 (KCNA1)
ACETAZOLAMINE ​
250mg BID, can increased to 500mg BID
​
EA2 (CACNA1)
ACETAZOLAMIDE
250mg BID, can increased to 500mg BID
​
PRRT2
CARBAMAZEPINE
​
JOUBERT SYNDROME & RELATED DISORDERS
ACETAZOLAMIDE MAY BE USEFUL
​
SYMPTOMATIC TREATMENT
AMANTADINE
​
RILUZOLE
used in SCA, Friedreich's ataxia
​
BUSPIRONE
​
GABAPENTIN
​
PREGABALIN
​
ZOLPIDEM
​
LAMOTRIGINE
​
TOPIRAMATE
Can improve cerebellar tremors
​
DYSTONIA
ACUTE DYSTONIC REACTION
DIPHENHYDRAMINE (BENADRYL)
25mg tab
Anticholinergic/ Antihistaminic
PHENIRAMINE (AVIL)
25mg TAB/ 22.5mg /ml (IV)
Anticholinergic/ Antihistaminic
​
PROMETHAZINE
Anticholinergic/ Antihistaminic
Mild D2 antagonist
Can worsen dystonia
​
BENZTROPINE
0.5-2 mg BID
Anticholinergic
​
STATUS DYSTONICUS
DEFINITION
Status dystonicus is a movement disorder emergency clinically characterized by frequent or continuous episodes of severe generalized dystonia, leading to very high levels of serum creatine, and sometimes myoglobinuria due to rhabdomyolysis
PATIENTS OFTEN DEVELOP
(1)Bulbar weakness causing compromise of upper airway
(2) Impairment of respiratory function
(3) metabolic derangements
(4) pain and exhaustion
Children with secondary dystonia commonly affected. between the ages of 5–16 years
​
TRIGGERS
Infections, trauma, surgery, anesthesia, metabolic abnormalities, pain, stress, abrupt withdrawal of dystonia drugs, and introduction of chelation therapy in Wilson’s disease,
​
MANAGEMENT
(1) Fluid and airway management
(2) Sedation with midazolam
(3) Neuromuscular paralysis
(4) General anesthetic agent like Propofol
(5) Anticholinergic agents​
​
LAST RESORT
(1) Intrathecal Baclofen
(2) Globus Pallidus internus DBS
​
DIFFERENTIAL DIAGNOSIS
Neuroleptic malignant syndrome
Serotonin syndrome
Malignant hyperthermia
Acute dystonic reactions
Mental status is reduced in neuroleptic malignant syndrome and serotonin syndrome, but normal in status dystonicus. Malignant hyperthermia mostly occurs in peri-operative setting, with symptoms including hyperthermia and autonomic dysfunction.
​
SPECIFIC DYSTONIA THERAPY
PRIMARY DYSTONIA
DYT11
ZONISAMIDE
Start 50mg OD, then 50mg BID, then 100mg BID.​
Target dose of 300 mg/day in adults
​
DYT5
LEVODOPA
​
PAROXYSMAL DYSTONIA
ADCY5
CAFFEINE / ACETAZOLAMIDE/CLONAZEPAM/
DEEP BRAIN STIMULATION (DBS)
​
PRRT2
CARBAMAZEPINE
​
MR1 MUTATIONS
CLONAZEPAM
​
MITOCHONDRIAL
PYRUVATE DEHYDROGENASE DEFICIENCY
VITAMIN-B1
KETOGENIC DIET
​
DOPAMINE BIOAMINE DEFECTS AND TRANSPORTOPATHIES
GTPCH (AR)
HIGH DOSE LEVODOPA
​
GTPCH (AD)
EXCELLENT RESPONSE TO LEVODOPA
TYROSINE HYDROXYLASE - TYPE A
GOOD LEVODOPA RESPONSE
​
TYROSINE HYDROXYLASE - TYPE B
GOOD LEVODOPA RESPONSE
​
SEPIAPTERIN REDUCTASE DEFICIENCY
HIGH DOSE OF LEVODOPA
​
PTP SYNTHASE DEFICIENCY
EXCELLENT LEVODOPA RESPONSE
​
AADC DEFICIENCY
DOPAMINE AGONIST
MAO INHIBITORS
PYRIDOXINE 100-200MG/DAY
FOLIC ACID
​
DBS FOR GENETIC DYSTONIA
DBS GOOD BENEFIT
DYT-1 (TOR1)
TAF1
SCGE (DYT11)
GNAL
KMT2B
DBS VARIABLE BENEFIT
PANK2
THAP1
ATP1A3
PRKRA(DYT16)
​
DBS LESS LIKELY BENEFIT
GNAO1
GNB1
VPS16
WILSON DISEASES
Anecdotal reports of positive results.
AICARDI GOUTIERES DISEASE
STN DBS useful in 1 case
​
TARGET FOR DBS
GPi was the target in over 90% of DBS placements.
STN was used for 17% of those with PKAN dystonia, 33% of those with RDP dystonia, and one confirmed case of DRD dystonia.
​
AUTOIMMUNE ENCEPHALITIS
LAB
ANTIBODIES IN SERUM (HIGHER SENSITIVITY THAN CSF)
LGI1
AQUAPORIN
MOG
​
ANTIBODIES IN CSF (HIGHER SENSITIVITY THAN SERUM)
NMDA
GFAP
NEUROFILAMENT AB.
​
PET-CT NEG (15%)
THYMOMA
SEMINOMA
TERATOMA
​
ANTIBODY POSITIVE CASES
Continue immunomodulation for 2 or more years
Recurrence in antibodies positive cases: 10-30%,
​
ANTIBODIES NEGATIVE AND CSF NORMAL BUT CLINICALLY EVIDENCE OF AI
Full dose of steroids for 1 month followed by taper
Long term immunosuppression to be started after second event or if first event was severe
​
RITUXIMAB (2ND LINE)
Start early if first line treatment not effective
​
COGNITION
PARKINSON'S DISEASE DEMENTIA
RIVASTIGMINE
Start with 1.5mg BID
Maximum 6mg BID
​
DONEPEZIL​
10mg HS
​
APHASIA (DEMENTIA (PPA)/ STROKE)
MEMANTINE
​
BROMOCRIPTINE
​
APRAXIA (DEMENTIA/ STROKE)
MEMANTINE
​
DONEPEZIL
AMANTADINE
POST STROKE HEMINEGLECT
DONEPEZIL
EXECUTIVE DYSFUNCTION
DONEPEZIL
​
AMANTADINE
METHYLPHENIDATE
​
PERSEVERATION/ IMPUSIVITY
SSRI​
​
​
CHOREA
RISPERIDONE
Starting dose 0.25mg BID
​
QUETIAPINE
Starting dose 25mg HS
​
TETRABENAZINE
Starting dose 25mg BID
​
GABAPENTIN
Starting dose 300mg BID
​
VALPROATE
Starting dose 200mg BID
​
CLONAZEPAM
Starting dose 0.5mg BID
​
WILSON'S DISEASE DIAGNOSIS
FALSE +VE URINARY COPPER
ACUTE LIVER DISEASE
ACUTE ON CHRONIC LIVER DISEASE
(WILL HAVE NORMAL CERULOPLASMIN)
SEVERE LIVER DISEASE
NEPHROTIC SYNDROME/ PROTEINURIA
NORMAL CERULOPLASMIN IN WILSON
5% OF HOMOZYGOTES
10-50% OF PATIENTS WITH LIVER DISEASE
ACUTE PHASE REACTANT
LOW CERULOPLASMIN
HYPO PROTEIN STATE
FREE CU = TOTAL SR CU - 3X CERUL (MG/DL)
NORMAL <15 MCGM/ DL
​
MEDNIK
MR/ ENTEROPATHY /DEAFNESS ICHTHYOSIS/ KERATODERMA
LOW SERUM CU AND CERULOPLASMIN WITH HIGH URINE CU
NPC
LOW SERUM CU AND CERULOPLASMIN
​
​
​
​
WILSON'S DISEASE
LAB DIAGNOSIS
ATP7B mutation
Urinary copper level
>100 microgram /24 hrs
>40 microgram / 24 hrs (children)
Serum Ceruloplasmin level
< 20 mg/ dl
In the absence of Kayser–Fleischer's rings, a liver biopsy with copper quantification is mandatory to confirm the diagnosis.
​
FALSE +VE URINARY COPPER
Acute liver disease
Acute on chronic liver disease (Normal Ceruloplasmin)
Severe liver disease
Nephrotic syndrome/ proteinuria
​
NORMAL CERULOPLASMIN IN WILSON
5% of homozygotes
10-50% of patients with liver disease
Acute phase reactant
​
OTHER LOW SERUM CERULOPLASMIN CAUSES
HYPO PROTEIN STATE
MEDNIK
Low Serum Copper
Low Ceruloplasmin
High Urine copper
NPC
Low Serum Copper
Low Ceruloplasmin
TREATMENT
INITIATION PHASE
PENICILLAMINE
Starting dose 250 mg/day
Increase by 250 mg every 2 weeks
SIDE EFFECTS OF PENICILLAMINE
Hypersensitivity: Fever, skin rash, lymphadenopathy
Thrombocytopenia, pancytopenia
Neurological deterioration
Kidney (late): Glomerulonephritis/ Good pasture syndrome
Skin: Bruising/ Elastosis performance serpiginosa
MAINTAINANCE PHASE:
Almost Complete recovery and Liver stabilization
Reduce the dose of PENICILLAMINE by 50%
ZINC (elemental) 50 mg TID
MONITORING AND THERAPY COMPLIANCE:
Non Compliance/ Over treatment
Urinary copper <300 microgram / 24 hrs:
Serum NCBC
NCBC (mg/dL) =
Total serum copper (mcg/dL) – 3.12 x serum Ceruloplasmin (mg/dL).
<5 mcg /dL: over treatment
>15 mg/dL: noncompliance.
PREGNANCY:
PENICILLAMINE
Dose reduced by 25% in first trimester
No breast feeding
​
​
​
ORAL MEDICATIONS FOR DYSTONIA
LEVODOPA/ CARBIDOPA
Can go upto 2 tab (100/25) TID​
​
TRIHEXYPHENIDYL
Start 2.0 mg at bedtime
Titrating slowly up to 40–50 mg/day (given TID) in children
Usually not tolerated above 20 mg/day in adults
​
BACLOFEN
80 mg/day maximum dose, given TID
TETRABENAZINE
12.5 mg titrated up slowly to 25–100 mg/day,
usually given TID
DIAZEPAM
10–60 mg/day, Given TID
​
CLONAZEPAM
1–4 mg/day, given BID
​
​
ESSENTIAL TREMORS
PROPRANOLOL (LEVEL A)
​
TOPIRAMATE (LEVEL A)
PRIMIDONE (LEVEL A)
BENZODIAZEPINE (LEVEL B)
GABAPENTIN (LEVEL B)
ATENOLOL (LEVEL B)
SOTALOL (LEVEL B)
BOTULINUM TOXIN (POSSIBLY USEFUL)
​
HEAD TREMOR
PROPRANOLOL (LEVEL B)
​
BOTULINUM TOXIN
​
​
NEUROLEPTIC MALIGNANT SYNDROME
ALTERED SENSORIUM/ MUTISM
FEVER/ AUTONOMIC INSTABILITY
RIGIDITY/ TREMOR/ DYSTONIA/ CHOREA
DYSPHAGIA/ DYSPNOEA/ TACHYPNOEA/ HYPOXIA
LAB: ELEVATED CPK > 3X
LEUKOCYTOSIS
​
MANAGEMENT
MAINTAIN HYDRATION
BROMOCRIPTINE
Starting dose 2.5MG BID
​
DANTROLENE
​
BENZODIAZEPINE
AMANTADINE
​
AUTONOMIC DYSFUNCTION
ORTHOSTATIC HYPOTENSION
FLUDROCORTISONE
0.1-0.4 mg (PER DOSE, OD)​
​
MIDODRINE
2.5 - 10 mg (PER DOSE, TID)
DROXIDOPA
100 - 600 mg (PER DOSE, TID)
Norepinephrine precursor​
​
PYRIDOSTIGMINE
60 mg (PER DOSE, TID)
​
ATOMOXETINE
18MG (PER DOSE, OD)
Inhibits presynaptic uptake of NE
​
POSTPRANDIAL HYPOTENSION
OCTREOTIDE
25 - 50 mcgm
Given before meals
​
ACARBOSE
5-50 mg
Given before meals
​
SUPINE HYPERTENSION
CLONIDINE
0.1 - 0.3mg
HYDRALAZINE
25-50mg
LOSARTAN
25mg
NITROGLYCERINE
NITRODERM TTS 5 (5mg/24HR)
Patch at night and remove in morning
SILDENAFIL
25mg
HEAD END ELEVATION
BEDTIME SNACK
​
ERECTILE DYSFUNCTION
SILDENAFIL
50 - 100mg PRN
TADALAFIL
5-20mg PRN
VARDENAFIL
5-20mg PRN
​
​
ETHANOL OR GHB RESPONSIVE DISORDERS
TREMOR
ESSENTIAL TREMOR
​
ISOLATED VOCAL TREMOR
​
PRIMARY WRITING TREMOR
​
ORTHOSTATIC TREMOR
​
TREMOR IN KENEDY'S DISEASE (SMA)
​
MYOCLONUS
DYT11 (SCGE)
​
POST HYPOXIC MYOCLONUS
​
UNVERRICHT LUNDBORG DISEASE
​
SIALIDOSIS TYPE1 (ADULT ONSET)
​
DYSTONIA
ABDUCTOR SPASMODIC DYSPHONIA
ADDUCTOR SPASMODIC DYSPHONIA
DYT4
DYT5
​
STIFF PERSON SYNDROME
Therapeutic trial of diazepam: starting dose of 5 mg 2-3 times daily Doses achieved may be as high as 120 mg per day.
MAINTAINANCE DOSE:
DIAZEPAM
20 to 80 mg/day in three or four divided oral doses
Daily doses of diazepam to control symptoms can be as high as 100 to 200 mg/day. If no improvement is noted with high doses of around 60 - 80 mg per day, replace with shorter-acting drugs such as Lorazepam in equivalent doses.
​
CLONAZEPAM
1 to 3 mg orally two to four times daily.
Started when Diazepam is not tolerated.
​
SECOND LINE TREATMENT
BACLOFEN
​
IMMUNOGLOBULINS
RITUXIMAB
​
TICS​
CLONAZEPAM
Start with 0.25mg BID
​
CLONIDINE
Start with 0.1mg 0.5 tab OD
​
TETRABENAZINE
Start with 25mg 0.5tab BI