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Neuroimmunology Lab

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Neuroimmunology laboratory under the department of neurology at AIMS, Kochi is the first of its kind in India- a dedicated comprehensive testing facility for autoimmune neurological disorders under a trained clinical autoimmune neurologist. Autoimmune neurology is the twenty-first century sub specialty in neurology. It includes disorders of all other sub specialties of neurology like epilepsy, movement disorder, cognition, neuromuscular but with an autoimmune etiology. These disorders can be associated with a cancer (paraneoplastic) as well without cancer association (non paraneoplastic).

These disorders are under diagnosed and often misdiagnosed. Many a times, these diseases are misdiagnosed as "neurodegenerative disorders" which means practically no effective treatment available. But in fact, if properly investigated with appropriate tools (which include disease marker testing in a neuroimmunology lab) and diagnosed as an autoimmune neurological syndrome, it becomes potentially treatable and often fully reversible. Early diagnosis is the key factor in recovery. Here comes the importance of comprehensive neuroimmunology service which can provide an early diagnosis.

Aim

Lack of testing facilities for markers of the disease and lack of awareness among care givers are the two important limitations in diagnosing and treating these diseases. Our aim is to provide a world class testing facility, define the spectrum of these disorders in our country as well as to disseminate information among the physician community. We are planning to do research on discovering new disease markers, to develop a nation wide registry for autoimmune neurological disorders and to develop a bio bank for these disorders in collaborations with physicians and institutions across the country.

Currently this laboratory conducts tests for paraneoplastic panel of neuronal antibodies, NMO (AQP4)antibodies,Voltage gated potassium channel antibodies-CASPR 2 and LGI1, NMDA receptor antibody.

We are planning to expand the spectrum to include GAD 65 antibody, Acetyl choline receptor antibody, Anti Musk antibodies, Anti MAG antibodies, CSF oligoclonal bands, Striational muscle antibody, GABA B antibodies, glycine antibodies, Voltage gated calcium channel antibodies (VGCC) P/Q &N, Alpha 3ganglionic acetyl choline receptor and Basal ganglia antibodies.

When to suspect autoimmune etiology?

The spectrum of autoimmune neurology is ever expanding. Starting with the traditional spectrum like Guillan-Barre syndrome, Myasthenia gravis, CIDP, vasculitis, ADEM, paraneoplastic neurological syndromes and NMO, now it has expanded to include autoimmune encephalitis, autoimmune dementia, autoimmune epilepsy, autoimmune ataxia and myelopathy, autoimmune brainstem encephalitis, NMO spectrum of disorders and autoimmune movement disorders. Virtually any part of central nervous system, autonomic nervous system, peripheral nervous system and muscle can be involved. They can present in any clinical form-from cortex down to skeletal muscle and autonomic nervous system dysfunction. High index of clinical suspicion is the earliest step in making an early diagnosis and treatment.

Here is a rough guideline about when to suspect an autoimmune neurological disorder-The clinical presentation can range from encephalitis, seizures, cognitive decline, optic neuritis, stroke like episodes, behavioral symptoms like psychosis, brainstem encephalitis characterized by cranial nerve and pyramidal involvement, ataxia, movement disorders like chorea and myoclonus ,dyskinesias, cerebellar ataxia, myelopathy, plexopathy, radiculopathy, neuropathy, autonomic neuropathy, myopathy and neuromuscular conduction defect-myasthenia

Though the classical description of VGKC is limbic encephalitis and Moorvan's syndrome,the other presentations like PCD, GI dysmotility, parkinsonism, tremor, chorea, sensory motor neuropathy, hyponatremias, dyssomnia , hyperphagia, facio brachial dystonic seizure, other seizures and presentation mimicking CJD are well described.

NMDA receptor antibodies classically associated with Psychiatric features and memory loss, orofacial dyskinesia, choreoathetoid movements, abnormal posturing or increased tone, catatonic state and central hypoventilation.

NMO IgG has expanded the spectrum of NMO to include optic neuritis and myelitis into NMO spectrum of disorder without the classical presentation of eye and spine involvement.

Clinical features

History

Clinical examination

  • History or family history of cancer
  • History or family history of systemic autoimmunity
  • History of chronic smoking
  • Elderly age group
  • History of cachexia, anorexia and fever
  • Sub acute onset<12 weeks
  • Multifocal involvement
  • Significant autonomic involvement
  • Features of systemic autoimmunity

Laboratory

Radiological

  • Inflammatory CSF
  • Elevated CSF protein
  • OCB
  • Markers of systemic autoimmunity
  • Limbic encephalitis
  • Longituidinally extensive transverse myelitis
  • Longituidinal signal changes in spinal tracts

Autoimmune etiology should be strongly sought in all neurological syndromes of unexplained etiology.

Paraneoplastic/autoimmune etiology should be considered in subacute sensory neuronopathy, cerebellar ataxia, limbic encephalitis, opscoclonus/myoclonus, encephalomyelitis, chronic gastrointestinal pseudo obstruction and Lambert Eaton myasthenic syndrome.

However remember that atypical presentations are more common in these disorders. Course can be variable. In view of the treatablitiy and reversibility of the condition as well as the easy availability of an affordable treatment, autoimmune evaluation should be considered in other cases also.

Paraneoplastic antibodies are cancer specific, not disease specific. Hence we discourage testing for single antibodies in the panel. Some times same patient can have multiple antibodies which in fact help us to locate cancer easily.

Details of the tests available are given below.

1. Paraneoplastic panel of neuronal antibodies. (Indirect Immunofluroscence testing and confirmation by immune dot blot)

This tests serum and CSF for

1. ANNA-1 (anti Hu)- antineuronal nuclear antibody 1

2. ANNA-2 (anti Ri)- antineuronal nuclear antibody 2

3. ANNA-3 -antineuronal nuclear antibody 3

4. AGNA-1 Anti Glial nuclear antibody-1

5. PCA-1 (anti Yo) - anti Purkinje cell cytoplasmic antibody-1

6. PCA-2 anti Purkinje cell cytoplasmic antibody-2

7. PCA-Tr- anti Purkinje cell cytoplasmic antibody Tr,

8. Anti Amphiphysin antibody

9. Anti CRMP-5 {Collapsin Response Mediator Protein-5} (Anti CV-2 ) antibody

10. Anti Ma/Ta antibody.

2. Voltage gated potassium channel antibody (VGKC)- (Indirect Immunofluroscence testing)

1. LGI-1 (Leucine rich glioma inactivated protein -1)

2. CASPR-2 (Contactin associated protein-2)

3. NMDA (N- methyl –D-aspartate) receptor antibody (Indirect Immunofluroscence testing)

4. NMO-IgG (Aquaporin-4) antibody (Indirect Immunofluroscence testing)

Specimen: Serum or CSF (Volume 3ml)

Please send relevant clinical information, investigation details, name, phone number, email and contact address of referring physician.

Method of sample transportation

Use a screw top, leak proof container. Sample is stable at ambient temperature for 72 hours. By courier, should reach the lab within 72 hours. Avoid sending the sample at weekends to reduce the transport time to less than 72 hours. If any delay is expected, send samples refrigerated at 4 degree Celsius which is stable upto 14 days. Store sample in a refrigerator until sending. In case of small sample volume or any other problem, contact lab before sending.

Pro premium plan of Professional couriers is fast and economic option (next day afternoon delivery at AIMS, Kochi).

Method of payment

Demand Draft to Amrita Institute of Medical Sciences payable at Kochi

Call or write for any clarifications regarding sample collection, storing, sending, applying or interpreting a result.

Reporting time: Tests are performed every 2 weeks (Maximum laboratory time)

Working hours 8.30 am to 5.30pm. Sunday holiday.

Address for sending Samples

Dr. Sudheeran Kannoth,
Neuroimmunology lab (T6F3)
Amrita Institute of Medical Sciences(AIMS)
Ponekkara PO, Kochi, 682041
Kerala,India.
Phone: 0091 484 280 1234, 0091 484 285 1234,
0091 484 668 1234

(4 line to AIMS exchange) Extension- 2916 & 6318.

Mobile no. : 09400998656 (Dr. Annamma Mathai-on call mobile)

Email : neuroimmunology@aims.amrita.edu

References:

Paraneoplastic syndromes in general

Kannoth.S.Paraneoplastic neurologic syndrome:A practical approach.Ann Indian Acad Neurol 1.(2012) 6-12

Different antibodies

ANNA-1(anti Hu)- antineuronal nuclear antibody 1

Lucchinetti CF, Kimmel DW, Lennon VA. Paraneoplastic and oncological profiles of patients seropositive for type 1 anti-neuronal nuclear auto antibodies. Neurology 1998; 50:652-657

ANNA-2(anti Ri)- antineuronal nuclear antibody 2

Pittock SJ, Lucchinetti CF, Lennon VA. Anti-neuronal nuclear autoantibody type 2: Paraneoplastic accompaniments. Ann Neurol 2003; 53:580-597.

ANNA-3 (antineuronal nuclear antibody 3)

Chan KH, Vernino S, Lennon VA. ANNA-3 anti-neuronal nuclear antibody: Marker of lung cancer-related autoimmunity. Ann Neurol 2001; 50:301-311.

AGNA-1 (Anti Glial nuclear antibody-1)

Graus F,Vincent A,Pozo –Rosich P et al. Antiglial nuclear antibody :Marker of lung cancer - related paraneoplastic neurological syndromes.J Neuroimm 2005 ; 165 :166-71

PCA-1 (anti Yo) (anti Purkinje cell cytoplasmic antibody-1)

Peterson K, Rosenblum MK, Kotanides H, Posner JB. Paraneoplastic cerebellar degeneration. I. A clinical analysis of 55 anti-Yo antibody-positive patients. Neurology 1992; 42:1931-1937.

PCA-2 (anti Purkinje cell cytoplasmic antibody-2)

Vernino S, Lennon VA. New Purkinje cell antibody (PCA-2): marker of lung cancer-related neurological autoimmunity. Ann Neurol 2000; 47:297-305.

PCA-Tr- (anti Purkinje cell cytoplasmic antibody Tr)

Bernal F, Shams'ili S, Rojas I et al: Anti-Tr antibodies as markers of paraneoplastic cerebellar degeneration and Hodgkin's disease. Neurology 2003; 60:230-234.

Anti Amphiphysin antibody

Pittock SJ, Lucchinetti CF, Parisi JE, et al.Amphiphysin autoimmunity: Paraneoplastic accompaniments. Ann Neurol. 2005; 58:96-107.

AntiCRMP-5 {Collapsin Response Mediator Protein-5} (Anti CV-2) antibody

Yu Z, Kryzer TJ, Griesmann GE, Kim K, Benarroch EE, Lennon VA. CRMP-5 neuronal autoantibody: marker of lung cancer and thymoma-related autoimmunity. Ann Neurol 2001; 49:146-154.

Anti Ma/Ta antibody

Dalmau J. Graus F. Villarejo A. et al.Clinical analysis of anti-Ma2-associated encephalitis. Brain 2004; 127(Pt 8):1831-44.

Voltage gated potassium channel antibody (VGKC). LGI-1 (Leucine rich glioma inactivated protein-1). CASPR-2 (Contactin associated protein-2)

1.Irani SR, Alexander S, Waters P et al. Antibodies to Kv1 potassium channel-complex proteins leucine-rich, glioma inactivated 1 protein and contactin-associated protein-2 in limbic encephalitis, Morvan's syndrome and acquired neuromyotonia. Brain. 2010; 133 :2734-48.

2.Lai M, Huijbers MG, Lancaster E et al. Investigation of LGI1 as the antigen in limbic encephalitis previously attributed to potassium channels: a case series. Lancet Neurol. 2010; 9:776-85.

NMDA (N- methyl –D-aspartate) receptor antibody

Dalmau J, Lancaster E, Martinez-Hernandez E, Rosenfeld MR, Balice-Gordon R.Clinical experience and laboratory investigations in patients with anti-NMDAR encephalitis.Lancet Neurol. 2011;10:63-74.

NMO-IgG(Aquaporin-4) antibody

Jacob A, McKeon .A, Nakashima I, Sato DK, Elsone L, Fujihara., de Seze .J.Current concept of neuromyelitis optica (NMO) and NMO spectrum disorders J Neurol Neurosurg Psychiatry jnnp-2012-302310Published Online First: 10 November 2012 doi:10.1136/jnnp-2012-302310.

Useful links for information:

http://www.pnseuronet.org/

http://www.esni.org/

http://www.birmingham.ac.uk/facilities/clinical-immunology-services/neuroimmunology/index.aspx

http://www.isniweb.org/

Doctors / Faculties-Neuroimmunology Lab