sensory ataxia

Approach to sensory ataxia

Susanth MJ

1

Ataxia

• Greek ‘taxis’ = order

• Incoordination without significant weakness

• Impaired balance and/or directional limb movements

and/or dysarthria

• Result from cerebellar, vestibular or sensory disorders

2

Visual impulses from

retinae

Proprioception from ocular

musclesjudge the distance of objects from

the body

LabyrinthsChanges in the velocity of

motion and position of the

body

Proprioceptors of the joints

and muscles esp neck

Reflex, postural, and

volitional movements

Cerebellar &

Brainstem

Structures

Maintenance of Equilibrium

Proprioceptors

• Position of our body or parts of our body

• Force, direction, and range of movement of

the joints (kinesthetic sense)

• Sense of pressure, both painful and

painless

4

Proprioceptive fibers predominantly in

motor nerves

Dorsal root gangliaCell bodies of all the sensory

neurons Posterior (Dorsal) Roots

Posterior

Columns

Somatotopic laminations in the posterior column

5

Posterior column sensations

• Touch-pressure

• Vibration

• Direction of movement and position of

joints

• Stereoesthesia - recognition of surface

texture, shape, numbers, and figures

written on the skin

• Two-point discrimination6

Depend on

patterns of

touch-pressure

Other mediators of proprioception in the spinal cord

• Cells in the more loosely

structured "reticular" part of the

dorsal column nuclei that receive

secondary ascending fibers from

the dorsal horns of the spinal

cord

• Project to brainstem nuclei,

cerebellum, and thalamic nuclei

Clinical Testing of Sensory Ataxia

Proprioception

• Awareness of the position and movements of our limbs, fingers, and

toes

Two modalities comprising proprioception

• Sense of position

• Sense of movement

– Normally, a very slight degree of movement is appreciated in the

digits (as little as 1 degree of an arc)

– Rapid movements are more easily detected than are slow ones

8

Usually lost together

Clinical situations occurs where position is

lost but movement (kinesthesia) is retained

Opposite occurs but is infrequent


Pseudoathetosis

• "piano-playing" movements

• When the patient has his arms

outstretched and eyes closed,

the affected arm will wander

from its original position

9


Romberg sign

• Compares balance as the patient stands with eyes

open and eyes closed

• Only a marked discrepancy in balance with eyes open

and with eyes closed qualifies as a Romberg sign

• Mild degrees of unsteadiness in a nervous or

suggestible patient may be overcome by diverting his

attention10


Romberg sign

• Most certain indication of abnormality is the need to

step to the side or backward to avoid falling

• Positive due to sensory ataxia, vestibulopathy, or

motor disorder

• May be difficult to perform or interpret in a grossly

ataxic patient with a cerebellar disorder

11


Testing of Vibratory Sense

• Composite sensation comprising touch and rapid alterations of

deep-pressure sense

• Only cutaneous structure capable of registering such stimuli of

this frequency is the rapidly adapting pacinian corpuscle

• Conduction of vibratory sense depends on both cutaneous and

deep afferent fibers

– Rarely affected by lesions of single nerves but will be

disturbed in patients with disease of multiple peripheral

nerves, dorsal columns, medial lemniscus, and thalamus12


Testing of Vibratory Sense

• Vibration and position sense are usually lost together

• One of them (most often vibration sense) may be

affected disproportionately

• With advancing age, vibration is the sensation most

commonly diminished, especially at the toes and

ankles

13

Sensory ataxia

Worth considering in any patient with ataxia who

has

• No nystagmus or cerebellar dysarthria.

• Romberg’s sign

• Pseudoathetosis,

• Impaired joint position or vibration sense

14

Sensory ataxia Vs Cerebellar Ataxia

• Sensory ataxia is often mistaken for cerebellar ataxia,

leading to diagnostic errors and delays

• Cerebellar ataxia is more common and easier to

identify with certainty

• ‘Sensory ataxia-plus’ syndromes may have a

component of cerebellar ataxia

15

Clinical differences between sensory and cerebellarataxia

Sensory ataxia Cerebellar ataxia

Nystagmus Absent Except sensory

ataxia-plus syndromes

Present

Dysarthria Absent Scanning/staccato

speech

Eye movements Sometimes abnormal

(eg, CANOMAD)

Normal/slow

Finger–nose ataxia Present (significantly

worse with eye closure)

Present

16



Heel–shin ataxia Present (significantly

worse with eye

closure)

Present

Deep tendon reflexes Absent/present Normal/pendular

Joint position sense Impaired Normal

Pseudoathetosis Usually present Absent

Exteroceptive

sensation

Reduced Normal

17



Romberg’s sign Positive Classically negative

Gait High stepping

(stamping)/unsteady

Broad-based,

staggering

18

Proposed criteria for diagnosing clinically probable sensory ataxia

1. Ataxia confirmed by clinical examination:

– Finger–nose incoordination and/ or heel–toe ataxia

and/or broad-based ataxic gait

2. Two or more of:

a) Romberg’s sign or ataxia significantly worse with

eyes closed, or history of ‘wash basin sign’3

b) Pseudoathetosis and/or impaired joint position and/or

vibration sense/s.

c) Absence of nystagmus and/or cerebellar dysarthria.19

DDs Of Sensory Ataxia

• Pathology is most likely in the

proprioceptive system

• Anywhere in the pathway from the

peripheral sensory nerves, dorsal root

ganglia, sensory nerve roots, dorsal

column of spinal cord, medial

lemnisci of the brainstem and parietal

cortices

• Dorsal root ganglia is often the

major site of pathology

20


21

Secondary To Peripheral Neuropathies

Paresthesia, tingling, Pseudocramp

Symmetrical distal sensory loss

Areflexia or hyporeflexia

Weakness, if present, symmetrical

When the neuropathy is primarily

demyelinating rather than axonal,

paresthesia is an early feature


22

Acute

Miller Fisher syndrome

Sensory variant of GBS

Semisynthetic penicillins

Subacute Lyme disease

Neurosarcoidosis

Chronic

CIDP

Paraproteinaemia

Diabetes mellitus

Coeliac disease

Vitamin E deficiency

Secondary To Peripheral Neuropathies

Miller Fisher syndrome

• Characterised by ophthalmoplegia, ataxia and

areflexia

• May be either antecedent infection (mainly

Campylobacter jejuni and Haemophilus influenzae)

and/or underlying autoimmune or neoplastic disorder

• Serum anti-GQ1b IgG antibody titre is elevated in

over 80% of cases

23

Sensory variant of Guillain–Barré syndrome

• Rare

• Solely involves the large sensory fibres

• Sensory ataxia, impaired joint position and vibration

sense and areflexia, but usually normal strength

• Serum antibodies to GD1b and GQ1b gangliosides

may be positive

24

MFS and Sensory GBS

NCS

• Both may show demyelinating polyradiculoneuropathy

• MFS may often have either normal or show small

SNAPs

CSF

• Normal cell count but raised protein

25

CIDP

• Typically presents with monophasic, relapsing or

progressive symmetrical sensory and motor neuropathy

• Evolving over 8 weeks

• Paraesthesia, proximal weakness without wasting,

areflexia and loss of vibration and/or joint position sense

• NCS may show either conduction slowed to the

demyelinating range or partial conduction block

26

Sensory Ataxic form of CIDP

• Uncommon

• Manifests as prominent numbness in the extremities,

ataxia, areflexia and impaired vibration and/or joint

position sense

• Weakness may be mild or absent

27

Sensory Ataxic form of CIDP

• NCS show motor abnormalities typical of CIDP

• Nerve biopsy shows demyelination and remyelination

• Management is along lines similar to typical CIDP

• Often responds to corticosteroids and/or intravenous

immunoglobulins

28

It is worthwhile measuring antiganglioside antibodies in

all patients with otherwise idiopathic sensory ataxic

neuropathies, as intravenous immunoglobulin

treatment is often effective

29

Paraproteinaemic neuropathy

• Late onset slowly progressive, demyelinating neuropathy

• Distal and symmetrical, mainly sensory neuropathy.

• Monoclonal IgM antibodies against myelin-associated

glycoprotein

• Predominant impairment of joint position and vibration

sense

• May have tremor but little weakness.

30


• NCS usually show symmetrical and predominantly distal

demyelination with disproportionately prolonged distal

motor latencies

• History of diabetes mellitus and alcohol excess (both

common causes of neuropathy) do not preclude the

possibility of coexisting pathology

• Serum immunoelectrophoresis and immunofixation are,

therefore, important investigations in the diagnostic

workup of ataxic neuropathy

31

Waldenström’s macroglobulinaemia

• Lymphoplasmacytoid malignancy producing IgM paraprotein

• Can present with sensory ataxia if the IgM paraprotein shows

antimyelin-associated glycoprotein activity

CANOMAD

• Chronic Ataxic Neuropathy, Ophthalmoplegia, Monoclonal

IgM protein, Cold Agglutinins and AntiDisialosyl antibodies

• Associated with anti-GQ1b and antidisialosyl antibodies

32


Diabetic neuropathy

• Commonly presents with distal symmetrical polyneuropathy

• Small fibres are usually affected first, giving pain, burning,

impaired spinothalamic sensations and autonomic dysfunction.

• Large fibre sensation is affected later- develop paraesthesia

and gait imbalance.

• Often impaired vibration, joint position and pressure

sensations and loss of ankle reflex

• In advanced stage, there may be sensory ataxia

33

Coeliac ataxia

• Chronic inflammatory enteropathy

• Associated with sensitivity to ingested gluten.

• Neurological complications occur in 6–10%

– Ataxia and peripheral neuropathy are the common

presentations

– Ataxia may be cerebellar or sensory

34

Coeliac ataxia

Clinicians should request serum antigliadin antibodies

in patients presenting with sporadic idiopathic ataxia

35

Mitochondrial neuropathy

SANDO

Sensory Ataxic Neuropathy, Dysarthria and

Ophthalmoparesis

• Rare Triad due to mutations in polymerase gamma

(POLG) or TWINKLE genes

• As the clinical features include dysarthria, this leads

to confusion with cerebellar pathology

36


37

Subacute

HIV, HTLV-1, HCV

Small cell lung cancer

Pyridoxine intoxication

Chemotherapeutic agents

Thalidomide

Organophosphate exposure

Colonic carcinoma

Neuroendocrine tumour

Breast and ovarian cancer

Chronic Sjögren’s syndrome

Chronic active hepatitis

Due to Dorsal Root

Ganglionopathies

Dorsal Root Ganglionopathy

• Frequently associated with paraneoplastic disorders,

dysimmune conditions like Sjögren’s syndrome or

toxic exposure to drugs, such as chemotherapeutic

agents and pyridoxine

• Leads to degeneration of peripheral axons and central

sensory projections in the dorsal columns

• Unique pattern of non-length dependent sensory

nerve degeneration 38

Dorsal Root Ganglionopathy

• Asymmetric, patchy neuropathic symptoms of pain, burning,

paraesthesia and sensory loss, with predilection for upper

limbs

• Early sensory ataxia, areflexia, markedly impaired

proprioception, pseudoathetosis, but relatively preserved

muscle strength

NCS

• Often marked involvement of the sensory fibres, with reduced

or absent SNAPs in a non-length-dependent fashion

39

Paraneoplastic dorsal root ganglionopathy

• Subacute and rapidly progressive sensory ataxia, pain and

paraesthesia

• Most commonly associated with small cell lung cancer

• Other malignancies

– Colonic carcinoma

– Hodgkin’s lymphoma

– Neuroendocrine tumours

– Breast and ovarian carcinoma

40


• Associated with anti onconeural antibodies

• May develop before the cancer becomes clinically

overt

• Can antedate the cancer diagnosis by 0.5–62 months

41


Antionconeural Antibodies

• anti-Hu (antineuronal nuclear autoantibodies type 1)

– Most commonly associated antibody

– Sensitivity of 82% and specificity of 99%

Other antibodies

• antiamphyphysin

• anticollapsin response mediator protein-5 (CRMP-5)42

Immune mediated dorsal root ganglionopathy

Sjogren’s syndrome

• Lymphocytic infiltration in the dorsal root ganglion

• Present with dry eyes and dry mouth

• Lip biopsy can show destruction of small salivary

glands and inflammatory infiltrates

• Ganglionopathy almost always predates the diagnosis

of Sjögren’s syndrome

43

Sjogren’s syndrome

• Sensory symptoms of numbness, tingling, burning pain

and dysaesthesia

• Often asymmetric at onset

• Predominantly involve the upper limbs

• With progression, the symptoms and signs become

symmetrical and generalised

• Negative ANA/ENA (antinuclear antibody/extractable

nuclear antigen) (Anti-SSA (Ro))/SSB (La) antibodies)

does not exclude the diagnosis.44

Medication-induced dorsal root ganglionopathy

Pyridoxine overuse

• Pure sensory neuropathy with features of large fibre

involvement

• Rarely cause sensory dorsal root ganglionopathy

• Doses as little as 200 mgs per day may be the cause

45

Medication-induced dorsal root ganglionopathy

Anticancer drugs, particularly platinum compounds

like cisplatin

• Severity of neuropathy usually correlates with the

cumulative drug dose

• Coasting

– Sensory deficits may progress for several months

after stopping treatment

46

Infection-associated dorsal root ganglionopathy

HIV

• Most common infection associated with sensory

ataxia

• Typically presents acutely or subacutely.

• Peripheral neuropathy commonly associated

47

Infection-associated dorsal root ganglionopathy

Other infections causing sensory ataxia

• Hepatitis C

• Measles

• Epstein–Barr

• Varicella zoster

• Human T-cell lymphotropic virus type I

48

Chronic idiopathic ataxic neuropathy

• No identifiable cause

• Indolent, slowly progressive, dorsal root

ganglionopathy

• Normal strength with areflexia

• CSF, EMG and motor NCS are often normal, but

sensory potentials are absent

• Often refractory to treatment

49


50

Chronic

Chronic immune sensory

polyradiculopathy

Due to sensory nerve

root involvement

Severe sensory loss with preserved

sensory nerve action potentials

Chronic immune sensory polyradiculopathy

• Preferential involvement of the large myelinated

sensory nerve roots proximal to the dorsal root

ganglion.

• Presents with ataxia and limb paraesthesia.

• On examination sensory ataxia, areflexia, impaired

joint position and vibration sense but normal strength

51

Chronic immune sensory polyradiculopathy

• NCS normal, but somatosensory-evoked potentials are

abnormal, suggesting sensory root involvement

• MRI Lumbar spine may show enlarged and enhancing

nerve roots

• CSF may show raised protein

• Sensory rootlet biopsies may show demyelination similar

to CIDP

• May respond to immunomodulation52


53

Due to posterior spinal

column involvement

Paresthesias in the form of tingling and

pins-and-needles sensations or girdle- and

band-like sensations

Loss of vibratory and position sense

occurs below the level of the lesion

May simulate a parietal "cortical"

lesion, but differs in that vibratory sense

is also lost in spinal cord syndromes


54

Chronic

Vitamin B12 deficiency

Copper deficiency

Tabes dorsalis

HIV, HCV

Cervical myelopathy

Due to posterior spinal

column involvement


• Classical malabsorption disease uncommon

nowadays

• More likely occurs with

– Nitrous oxide exposure—anaesthesia and dental

staff or recreational abusers

– Gastric or ileal resections with bacterial

overgrowth in blind loops, anastomoses or

diverticula55


• Present with limb paraesthesia, subacute gait disorder

with sensory ataxia and/or spasticity

• Examination shows signs of dorsal column impairment,

including loss of proprioception and vibration as well as

the combination of sensory ataxia and spastic paraparesis.

• Length-dependent peripheral neuropathy often coexists

– May manifest as depressed lower limb reflexes with

stocking sensory loss56


• MR scan of spine may show increased T2 signal,

most commonly in the dorsal cervical and thoracic

cord

• May have normal or borderline B12 level

• Helpful tests to confirm the diagnosis

– Increased serum levels of homocysteine and

methylmalonic acid

57

Copper deficiency

• Under-recognised cause of neurological and

haematological abnormalities

Risk factors for copper deficiency

• Previous upper gastrointestinal surgery

• Zinc overload from zinc supplementation or ingestion

of denture cream

– Competes with copper for absorption

58

Copper deficiency

• Clinical picture is often clinically and radiologically

indistinguishable from vitamin B12 deficiency

• Anaemia (microcytic, macrocytic, or normocytic), leucopenia

and, rarely, thrombocytopenia. Plasma copper, caeruloplasmin

levels and urinary copper levels are all reduced

• Neurological syndrome is incapacitating and frequently

irreversible, especially if treatment is delayed

– Early diagnosis and treatment with copper supplementation

is therefore essential

59

HIV infection

• Can cause vacuolar myelopathy

• Causes symptoms in about 10% of patients with

AIDS, although half show pathological evidence at

autopsy.

• Often occurs in the late stages of HIV infection

• Commonly parallels the development of AIDS

dementia complex

60

HIV infection

• Slowly progressive painless spastic paraparesis,

sensory ataxia and sphincter dysfunction

• MR scan of the spine usually normal although there

may be non-specific tract hyperintensities

61

Tabes dorsalis

• In late-stage or tertiary neurosyphilis

• Degeneration of the dorsal columns of the spinal cord and

sensory nerve roots

• Lancinating or lightning-like pains, progressive sensory

ataxia, proprioceptive loss and positive Romberg’s sign

• Also by diabetes mellitus, vitamin B12 deficiency, and

other diseases that involve the posterior roots or dorsal

root ganglia62

Hepatitis C infection

• May cause transverse myelopathy

• Sensory ataxia may be its only manifestation

63

Compressive and demyelinating disorders

Cervical myelopathy

• Painful stiff neck, upper limb paraesthesia and gait and

balance disturbance

Other compressive pathologies (eg, meningioma)

• Cause sensory ataxia if there is predominant involvement

of the posterior columns

• Spastic weakness in limbs, impaired joint position and

vibration sense as well as a positive romberg sign64

Compressive and demyelinating disorders

Multiple sclerosis

• Can cause sensory ataxia if demyelination involves

the central sensory pathways

65


66

Due to Thalamus lesions• Involvement of the VPL and

VPM nuclei of the thalamus

• Usually because of a vascular

lesion, less often because of a

tumor

• Position sense is affected more

frequently than any other

sensory function


67

Due to Parietal lesions•Loss of proprioceptive sensation,

or to lack of spatial orientation

•Due to the destruction of the

parietopontine fibres destined for

the cerebellum

•Can occur without any sensory

loss

Inherited causes of sensory ataxia

Complete absence of SNAPs in someone with no positive

sensory symptoms strongly suggests a genetic cause

• Friedreich’s ataxia

• Ataxia with vitamin E deficiency

• Abetalipoproteinaemia

• Spinocerebellar ataxia with neuropathy

• Mitochondrial neuropathies

68

Role Of Neurophysiology

• Slowing and reduced amplitude of SNAP

– Lesions of nerve or sensory ganglion

• Severe sensory loss with preserved sensory nerve action

potentials indicates a radiculopathy

• Suggest the pathological process, Axonal Versus

Demyelination.

• Neurophysiology can and should be repeated if the

clinical syndrome progresses or alters 69

Role Of Neurophysiology

Dorsal root ganglionopathy

• SNAPs may be more affected in the upper than the lower

limbs

• Non-length-dependent axonal degeneration helps to

distinguish DRG from the more common dying-back axonal

neuropathies

Sensory root involvement, as in chronic immune sensory

polyradiculopathy

• Normal nerve conduction, but often abnormal somatosensory-

evoked potentials70

To Detect And Diagnose Sensory Ataxias

• Initial differentiation relies heavily on a careful and

targeted clinical examination

• Subsequently detecting correct cause of sensory

ataxia by adopting a logical anatomical approach

• Requires neurophysiology

– into anatomical (nerve, dorsal root ganglion, etc.)

and pathological (demyelinating vs axonal) subsets

71

Other investigationsAetiology Ancillary investigations

Miller Fisher syndrome Anti-GQ1b antibodies, CSF, NCS

Sensory variant of GBS Anti-ganglioside antibodies, CSF, NCS

Lyme disease Lyme serology

Neurosarcoidosis CSF, NCS, ACE, chest X ray, HPE

CIDP NCS, CSF

Paraproteinaemia Electrophoresis, anti-MAG

Diabetes mellitus Plasma glucose.

Coeliac disease Anti-tTG antibodies

Vitamin E deficiency Serum vitamin E level 72

Other investigations

Aetiology Ancillary investigations

HIV, HTLV-1, HCV Serology

Paraneoplastic Anti-Hu, CRMP-5, Relevant imaging

Pyridoxine intoxication History of exposure; pyridoxine levels

Chemotherapeutic

agents

History of exposure

Sjögren’s syndrome ENA (Anti-SSA/SSB) Abs, Lip biopsy

Chronic active hepatitis RF, ANA, ASMA, hepatitis serology

73

Other investigations

Aetiology Ancillary investigations

CISP NCS, SSEP, CSF, MRI

Vitamin B12 deficiency Serum B12, Schilling’s test

Copper deficiency Serum copper and ceruloplasmin level.

Tabes dorsalis Syphilis serology

Cervical myelopathy Neuroimaging

74

Thank you

76

Clinical Approach To Ataxia

• First step is to distinguish cerebellar, sensory and

vestibular ataxia

77

sensory ataxia

Health & Medicine

original position

eyes open

eyes closedonly

range of movement

movement kinesthesia

dorsal column nuclei

slight degree of movement

brainstem nuclei