Sensory ataxia

1. Approach to sensory ataxia Susanth MJ 1

2. 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

3. Visual impulses from retinae Proprioception from ocular muscles judge the distance of objects from the body Labyrinths Changes 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

4. 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 ganglia Cell bodies of all the sensory neurons Posterior (Dorsal) Roots Posterior Columns

5. Somatotopic laminations in the posterior column 5

6. 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 discrimination 6 Depend on patterns of touch-pressure

7. 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

8. 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

9. Clinical Testing of Sensory Ataxia Pseudoathetosis "piano-playing" movements When the patient has his arms outstretched and eyes closed, the affected arm will wander from its original position 9

10. Clinical Testing of Sensory Ataxia 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 attention 10

11. Clinical Testing of Sensory Ataxia 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

12. Clinical Testing of Sensory Ataxia 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 thalamus 12

13. Clinical Testing of Sensory Ataxia 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

14. 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

15. 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

16. Clinical differences between sensory and cerebellar ataxia 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

17. Clinical differences between sensory and cerebellar ataxia Sensory ataxia Cerebellar ataxia 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

18. Clinical differences between sensory and cerebellar ataxia Sensory ataxia Cerebellar ataxia Romberg’s sign Positive Classically negative Gait High stepping (stamping)/unsteady Broad-based, staggering 18

19. Proposed criteria for diagnosing clinically probable sensory ataxia Ataxia confirmed by clinical examination: Finger–nose incoordination and/ or heel–toe ataxia and/or broad-based ataxic gait Two or more of: Romberg’s sign or ataxia significantly worse with eyes closed, or history of ‘wash basin sign’3 Pseudoathetosis and/or impaired joint position and/or vibration sense/s. Absence of nystagmus and/or cerebellar dysarthria . 19

20. 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. DDs Of Sensory Ataxia 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. DDs Of Sensory Ataxia 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

23. 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

24. 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

25. 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

26. 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

27. 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

28. 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

29. It is worthwhile measuring antiganglioside antibodies in all patients with otherwise idiopathic sensory ataxic neuropathies, as intravenous immunoglobulin treatment is often effective 29

30. 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

31. Paraproteinaemic neuropathy 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

32. Waldenström’s macroglobulinaemia Lymphoplasmacytoid malignancy producing IgM paraprotein Can present with sensory ataxia if the IgM paraprotein shows antimyelin -associated glycoprotein activity CANOMAD C hronic A taxic N europathy, O phthalmoplegia , M onoclonal IgM protein, Cold Agglutinins and A nti D isialosyl antibodies Associated with anti-GQ1b and antidisialosyl antibodies 32 Paraproteinaemic neuropathy

33. 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

34. 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

35. Coeliac ataxia Clinicians should request serum antigliadin antibodies in patients presenting with sporadic idiopathic ataxia 35

36. Mitochondrial neuropathy SANDO S ensory A taxic N europathy, D ysarthria and O phthalmoparesis 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. DDs Of Sensory Ataxia 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

38. 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

39. 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

40. 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

41. Paraneoplastic dorsal root ganglionopathy Associated with anti onconeural antibodies May develop before the cancer becomes clinically overt Can antedate the cancer diagnosis by 0.5–62 months 41

42. Paraneoplastic dorsal root ganglionopathy 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

43. 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

44. 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

45. 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

46. 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

47. Infection-associated dorsal root ganglionopathy HIV Most common infection associated with sensory ataxia Typically presents acutely or subacutely . Peripheral neuropathy commonly associated 47

48. 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

49. 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. DDs Of Sensory Ataxia 50 Chronic Chronic immune sensory polyradiculopathy Due to sensory nerve root involvement Severe sensory loss with preserved sensory nerve action potentials

51. 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

52. 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 immunomodulation 52

53. DDs Of Sensory Ataxia 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. DDs Of Sensory Ataxia 54 Chronic Vitamin B12 deficiency Copper deficiency Tabes dorsalis HIV, HCV Cervical myelopathy Due to posterior spinal column involvement

55. Vitamin B12 deficiency 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 diverticula 55

56. Vitamin B12 deficiency 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 loss 56

57. Vitamin B12 deficiency 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

58. 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

59. 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

60. 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

61. 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

62. 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 ganglia 62

63. Hepatitis C infection May cause transverse myelopathy Sensory ataxia may be its only manifestation 63

64. 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 sign 64

65. Compressive and demyelinating disorders Multiple sclerosis Can cause sensory ataxia if demyelination involves the central sensory pathways 65

66. DDs Of Sensory Ataxia 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. DDs Of Sensory Ataxia 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

68. 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

69. 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

70. 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 potentials 70

71. 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

72. Other investigations Aetiology 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

73. 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

74. 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

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76. Thank you 76

77. Clinical Approach To Ataxia First step is to distinguish cerebellar , sensory and vestibular ataxia 77