Approach to a patient with ataxia

Approach to a patient with ataxia

Dr Rakesh ShuklaProfessor Of Neurology

Definition

Ataxia (Gk. Taxis = Order; means lack of order) Ataxia denotes a syndrome of imbalance and incoordination involving gait, limbs, and speech and usually results from the disorder of the cerebellum or its connections It is characterized by dyssynergia, dysmetria, dysdiadochokinesia (Joseph Babinski). It is a disorder of rate, range, direction and force of movements (Gordon Holmes).

Outline of today’s lectureClinical ScenarioAnatomy and PhysiologyIs it Cerebellar AtaxiaHistory and ExaminationClassification Hereditary AtaxiasAcquired AtaxiasTreatmentConclusionMCQs

Clinical scenario

RK, 22 years young man presented with C/O headache, double vision, difficulty in walking 20-25 days

P/H RTA 3 mths back, tractor on which he was travelling overturned, No loss of consciousness, had a local penetrating injury in the nape of neck from a bolt in the tractor received local wound dressing, Eptoin (100g) 3HS

No H/o fever

O/E Afebrile vitals-normal, wt 43 kg GCS 15, fundus NAD

No sign of meningeal irritation, broad based gait ataxia, tandem walking impaired, Gaze evoked nystagmus +nt, broken smooth pursuit

Speech NAD, Romberg’s sign negative, no motor weakness, DTR normal, planter’s bilateral flexor

Diag Acute onset cerebellar syndrome presenting as gait ataxia

D/D chronic subdural haematoma, phenytoin intoxication

Clinical scenario

Investigation

HB 11 gm%, TLC 8,400 cells/cmm, DLC P58 L41E1, Platelet count 1.8 lac/cmm

Blood sugar-R 122mg/dl, S urea 15 mg/dl

S creatinine 0.8 mg/dl

Serum electrolytes, LFT normal

HIV, HbsAg, HCV-non reactive

PT/PC/ INR normal

Imaging: CECT scan brain

Imaging: MRI scan brain

Cerebellum has been recognised as a distinct division of the brain since Herophilus (335-280 BC) and Galen (131-200 AD)

Angevine et al., (1961) listed 24 different nomenclatures, terminology used by Larsell (1972) is used commonly at present.

It has a volume of about 144 cm3 and weighs 150g (~10% of brain weight), but its surface area is about 40% that of the cerebellar cortex.

Dorsal view of the cerebellum

Development of cerebellum

Vestibular proprioceptors provide information about the movement of head and its position. Having no limbs, primitive animals have only the flocculonodular lobe which coordinates the axial muscles that position the eyes, head and trunk

All higher animals having limbs have the anterior lobe to coordinate proprioceptive input from limbs and trunk. Emergence of vertical bipedal from the quadripedal posture places particular demands on gait coordination

The third and newest cerebral lobe (posterior lobe) expands in equal measure with the cerebrum, motor cortex, pyramidal tract, basis pontis

and inferior olivary nuclei

Cerebro-cerebello-cerebral circuit

Generalisations about cerebellar disease

Lesions Manifestations Lateralized Ipsilateral signs and symptoms Generalised Bilateral symmetrical symtomatology Acute Severe abnormalities at onset,

remarkable recovery with time Chronic Gradual progressive decline Vestibulo cerebellar Disequilibrium and an ataxic gait Vermis Truncal and gait ataxia Cerebellar hemispheres Appendicular ataxia

Differentiation of sensory and cerebellar ataxia

Sensory ataxia is due to severe sensory neuropathy, ganglinopathy or lesions of the posterior column of the spinal cord. e.g. Sjogren’s syndrome, cisplatin, CCNU, Para-neoplastic disorders, SACD, Tabes dorsalis.

Cerebellar ataxia Sensory ataxia

Scanning speech Normal speech

Nystagmus and other ocular signs Absent

Sensory exam normal, Romberg test negative

Sensory loss, Romberg’s test postive

Pendular reflexes Hypo to aeflexia

Reeling, ataxic gait Stamping gait

Differentiation of vestibular and cerebellar ataxia

Vestibular ataxia is due to lesion of vestibular pathways resulting in impairment & imbalance of vestibular inputs. e.g. vestibular, neuronitis, streptomycin toxicity.

Cerebellar ataxia Vestibular disorders

Sense of imbalance Vertigo and associated tinnitus and hearing loss

Past pointing is in the ipsilateral limb and in the direction of the lesion

Present in both the limbs and in the direction of the lesion

Gaze evoked rystagmus Direction of the rystagmus in away from the lesion

Scanning speech, intention tremors, dysdiadochokinesia, rebound phenomena, hypotonia and pendular reflexes

Absent

Differentiation between cerebellar and frontal lobe disorder

Frontal lobe ataxia (Brun’s ataxia) is due to involvement of

subcortical small vessels, Binswanger’s disease, multi infarct

state or NPH.

Cerebellar Frontal Lobes

Base of support Wide based Wide based

Velocity Variable Very slow

Stride Irregular, lurching Short, shuffling

Heal to shin Abnormal Normal

Initiation Normal Hesitant

Turns Unsteady Hesitant, Multistep

Postural instability * ****

Falls Late events Frequent

Important points in history

Age at onset

Mode of onset

Precipitating factors

Rate of progression

Symptoms of raised ICP

Presence of systemic symptoms

Drug history and toxin exposure

Family history

Examination

Neck tilt and titubation Nystagmus and other ocular movement abnormalities Dysarthria Intention tremor Hypotonia Past pointing Rebound phenomenon Macrographia Stance Ataxic Gait Pendular knee jerk

Individual with progressive ataxia

Negative FHAutosomal recessive or uncertain inheritance

Autosomal dominant inheritance

Exclude secondary causes

>25 years old

<25 years old

ARCAs, X-linked and mitochondrial inherited

Consider ADCAs

Test for:FRDA (GAA); AT (α-fetoprotein);

AVED (vit. E level); Refsum’s(phytanic acid); Wilson’s

Harding’s classification

Negative ADCA I(ataxia + CNS signs)SCA 1, 2, 3, 4, 8, 12,

17, and FGF 14

ADCA II(cerebellar syndrome +

pigmentary maculopathy)SCA 7

ADCA III(“pure” cerebellar

syndrome)SCA 5, 6, 10, 11,14, 15, and 22

Test for otherrecessiveataxias

Diagnosis of hereditary ataxia Insidious onset, symmetrical, and progressive

Age at onset

Early onset ataxia (age at onset below 25 years) is more likely to be consistent with autosomal recessive inheritance

Exceptions Friedreich’s ataxia, Tay Sachs disease

Late onset ataxia (age at onset over 25 years) is usual for those ataxias with dominant inheritance.

Exceptions, SCA7, DRPLA, EA-1, EA-2

Family history:- Direct questioning of patient and relatives.- H/o consanguinity- Pedigree charting- Negative family history does not exclude the diagnosis

Causes Of negative F/H

May be seen in - Adoption - Genetic non paternity - Anticipation - De novo mutation - Small family size - In X-linked inheritance only males are affected. - In mitochondrial disorders matrilineal mode of inheritance may be apparent although penetrance is

variable

Clinical features of Friedreich’s Ataxia

Autosomal recessive inheritanceOnset before 25 yearsProgressive limb and gait ataxiaAbsent DTR in legsElectrophysiological evidence of axonal sensory

neuropathyDysarthria*Areflexia in all four limbs*Distal loss of position and vibration sense*Extensor plantar responses*Pyramidal weakness of the legs*

*Develop within 5 years of onset of disease

Autosomal dominant ataxias

Heterogenous group of disorders with onset after 25 years

25 different genetic loci have been identified (SCA1 to SCA2)

Have diverse associated neurological features (retinopathy, optic atrophy, extra pyramidal or pyramidal signs, peripheral neuropathy, cognitive impairment, or epilepsy)

Most common forms-SCA1, SCA2 and SCA.

Bedside differentiation of SCAs

Large study n=526 patients (17 centres) with SCA 1,2, 3 or 6:- Pyramidal signs (67%) and brainstem oculomotor sign (74%) were most frequent in SCA 1- PN involvement was most frequent in SCA 2 (68%)- 24% of patients with SCA3 had dystonia

A decrease in visual (83%) and auditory (24%) acuity was the predominant sign in SCA7

No clinician can accurately distinguish between different polyglutamine expansion SCAs; but this form of SCA can be distinguished from other SCA types

David G, et al., Human Med Genet 1998; 7: 165-70Maschke M, et al., Mov Disord 2005; 20: 1405-12Schmitz-Hubsch T, et al., Neurology 2008; 71: 982-9

Clues to the SCAsClinical Features Genetic Forms

Age at onset Young adult: SCA 1, 2, 3, 21Older adult: SCA 6Childhood onset: SCA 7, 13, DRPLA

Upper motor neuron SCA 1, 3, 7, 12signs Some in SCA 6, 8

Rare in SCA 2Slow saccades Early, prominent: SCA 2, 7, 12

Late: SCA 1, 3Rare: SCA 6

Extra-pyramidal signs Early chorea: DRPLAAkinetic-rigid, Parkinson: SCA 2, 3, 21

Generalized areflexia SCA 2, 4, 19, 21Late: SCA 3Rare: SCA 1

Visual loss SCA 7Dementia Prominent: SCA 17, DRPLA

Early: SCA 2, 7Otherwise: rare

Myoclonus SCA 2, 14Tremor SCA 12, 16, 19Seizures SCA 10

Classification of acquired cerebellar ataxias

Ataxias due to toxic reasonsAlcoholic cerebellar degeneration (ACD)Ataxias due to other toxic reasons

Immune-mediated ataxiasParaneoplastic cerebellar degeneration (PCD)Other immune-mediated ataxias

Ataxias due to vitamin deficiency Ataxias due to other rare causes

Symmetrical acquired ataxias

Acute- Drugs: phenytoin, phenobarbitone, lithium,

Chemotherapeutic agents- Alcohol- Infectious: Acute viral cerebellitis, Post-infectious- Toxins: Toulene, glue, gasoline, methyl mercury

Subacute- Alcohol, or Nutritional (B1, B12)- Paraneoplastic- Antigliadin or anti GAD antibody- Prion diseases

Chronic- MSA-C- Hypothyroidism- Phenytoin toxicity

Asymmetrical acquired ataxias

Acute- Vascular: Cerebellar infarction or hemorrhage, Subdural Haemotoma- Infectious: Abscess

Subacute- Neoplastic : Glioma, metastates, lymphoma- Demyelination : MS- HIV related : Progressive multi-focal leuco-encephalopathy

Chronic- Congenital lesions: Arnold Chiari malformation, Dandy Walker syndrome

Tumors that produce ataxia

MedulloblastomaAstrocytomaEpendymomaHemangioblastomaMetastatic tumorMeningiomaCerebellopontine angle schwannoma

Sporadic ataxia

All acquired causes have been ruled out and there is no family history

A genetic explanation for “sporadic” ataxia is obtained in 4-22%

SCA6 is the most common dominant mutation detected in between 6% and 13% of patients

The frequency of the Freiedreich’s GAA expansion among cases of adult-onset is between 4 and 8%.

Treatment

Identify treatable causes of ataxia

No proven therapy for SCAs

Some patients with parameoplastic cerebellar syndrome improve following removal of tumour and immunotherapy

Preliminary evidence suggests that idebenone, a free radical scavenger improves myocardial hypertrophy

Genetic counselling can reduce risk in future generations

Treatable causes of ataxia

Hypothyroidism AVED Vitamin B12 deficiency Wilson’s Disease Ataxia with anti-gliadin antibodies and gluten senstive

enteropathy Ataxia due to malabsorption syndromes Lyme’s disease Mitochondrial encephalomyopathies, aminoacidopathies,

Leukodystrophies and urea cycle abnormalities

Conclusion Thorough history and examination is required

Age at onset and family history are most important

Hereditary ataixas can be divided into early onset (<25 years) or late onset (> 25 years)

Early onset ataxias are usually recessive, while late onset ataxias are usually dominant

Friedreich’s ataxia is the most common recessive disorder while SCA2 is the most common dominant disorder.

Contd…

No single physical sign is specific for a single disorder

Investigations should be performed in a logical order

Treatable causes should be excluded

Conclusion contd…

1. A horizontal gaze evoked nystagmus in which the direction of the fast phase reverses with sustained lateral gaze or beats transiently in the opposite direction when the eyes return to primary position is called

A. Periodic alternating nystagmusB. Seesaw nystagmusC. Rebound nystagmusD. Dysconjugate nystagmus

2. The typical signs of cerebellar herniation include the following EXCEPT

A. Stiff neckB. Alteration of consciousnessC. Ptosis and pupillary abnormalityD. Cardiac and respiratory abnormalities

3. Romberg’s sign is positive in which type of lesion :A. CerebellarB. Posterior columnC. HystericalD. Vestibular

4. Harding’s classification of cerebellar ataxia is based upon :A. Mode of inheritanceB. Site of involvementC. Chromosomal abnormalityD. Metabolic abnormality

5. Which statement is not true of Friedreich’s ataxia?A. Recessive inheritanceB.Dysarthria C. Flexor plantar responseD. Absent ankle jerk

6. Alcoholic cerebellar degeneration is characterized by :A. Gaze evoked nystagmusB. Limb ataxiaC. Gait ataxiaD. Action myoclonus

7. Cerebellar ataxia can result from intoxication with :A. LeadB. MercuryC. Manganese D. Gold

8. Wadia’s type of spinocerebellar degeneration is characterized byA. Limitation of downgazeB. Limitation of upgazeC. Slowing of saccadic movementsD. Broken smooth pursuit

9. Which of the following spinocerebellar ataxias (SCAs) has a similar ion channel, genetic and chromosomal abnormality as familial hemiplegic migraine

A. SCA type 2B. SCA type 4C. SCA type 6D. SCA type 8

10. A combination of ipsilateral oculomotor palsy and ipsilateral cerebellar ataxia is seen in which of the brainstem syndromes

A. ClaudeB. NothnagelC. WeberD. Benedikt

Approach to a patient with ataxia

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