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Neuroimmunology Laboratory

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Neuroimmunology laboratory under the department of neurology at Amrita Hospital, 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 laboratory) 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.

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, opsoclonus/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 treatability 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.

Investigations offered by the Neuroimmunology Laboratory

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

  • ANNA-1(anti Hu)- antineuronal nuclear antibody 1
  • ANNA-2(anti Ri)- antineuronal nuclear antibody 2
  • ANNA-3 -antineuronal nuclear antibody 3
  • AGNA-1 - Anti Glial nuclear antibody-1
  • PCA-1 (anti Yo) - anti Purkinje cell cytoplasmic antibody-1
  • PCA-2- anti Purkinje cell cytoplasmic antibody-2
  • PCA-Tr- anti Purkinje cell cytoplasmic antibody Tr,
  • Anti Amphiphysin antibody
  • Anti CRMP-5{Collapsin Response Mediator Protein-5} (Anti CV-2 ) antibody
  • Anti Ma/Ta antibody.

2. Paraneoplastic panel of neuronal antibodies in CSF (Indirect Immunofluorescence testing and confirmation by immune dot blot)

  • ANNA-1(anti Hu)- antineuronal nuclear antibody 1
  • ANNA-2(anti Ri)- antineuronal nuclear antibody 2
  • ANNA-3 -antineuronal nuclear antibody 3
  • AGNA-1 - Anti Glial nuclear antibody-1
  • PCA-1 (anti Yo) - anti Purkinje cell cytoplasmic antibody-1
  • PCA-2- anti Purkinje cell cytoplasmic antibody-2
  • PCA-Tr- anti Purkinje cell cytoplasmic antibody Tr,
  • Anti Amphiphysin antibody
  • Anti CRMP-5{Collapsin Response Mediator Protein-5} (Anti CV-2 ) antibody
  • Anti Ma/Ta antibody.

3. Voltage gated potassium channel antibody (VGKC)- in Serum (Indirect Immunofluorescence testing using transfected cells)

  • LGI-1 (Leucine rich glioma inactivated protein -1)
  • CASPR-2 (Contactine associated protein-2)

4. Voltage gated potassium channel antibody (VGKC)- in CSF (Indirect Immunofluorescence testing using transfected cells)

  • LGI-1 (Leucine rich glioma inactivated protein -1)
  • CASPR-2 (Contactine associated protein-2)

5. NMDA (N- methyal –D-aspartate) receptor antibody in Serum (Indirect Immunofluorescence testing using transfected cells)

6. NMDA (N- methyal –D-aspartate) receptor antibody in CSF (Indirect Immunofluorescence testing using transfected cells)

7. NMO-Ig G(Aquaporin-4) antibody in Serum (Indirect Immunofluorescence testing using transfected cells)

8. NMO-Ig G(Aquaporin-4) antibody in CSF (Indirect Immunofluorescence testing using transfected cells)

9. Autoimmune Encephalitis Panel of Antibodies in Serum (Indirect Immunofluorescence testing using transfected cells)

  • GABA B receptor
  • LGI 1protein
  • CASPR 2 protein
  • AMPA 1 receptor
  • AMPA 2 recepror
  • NMDA receptor

10. Autoimmune Encephalitis Panel of Antibodies in CSF (Indirect Immunofluorescence testing using transfected cells)

  • GABA B receptor
  • LGI 1protein
  • CASPR 2 protein
  • AMPA 1 receptor
  • AMPA 2 recepror
  • NMDA receptor

11. GABA B receptor antibody in Serum (Indirect Immunofluorescence testing using transfected cells)

12. GABA B receptor antibody in CSF (Indirect Immunofluorescence testing using transfected cells)

13. GAD 65 in Serum (Indirect ELISA)

14. Acetylcholine Receptor Autoantibody in serum(Indirect ELISA)

15. Multiple Sclerosis Evaluation Panel (Isoelectric Focusing and Immunoblotting method)

  • Serum Albumin
  • Serum IgG
  • CSF Albumin
  • CSF IgG
  • CSF IgG index
  • CSF IgG synthesis rate
  • OCB in CSF
  • OCB in Serum

Paired serum and CSF samples are necessary.

16. Ganglioside Antibody Evaluation Panel in serum (Immune dot blot method)

  • Anti Ganglioside IgG in serum( GM1, GM2, GM3, GD1a, GD1b, GT1b and GQ1b)
  • Anti Ganglioside IgM in serum.( GM1, GM2, GM3, GD1a, GD1b, GT1b and GQ1b)

17. MUSK antibody in serum (Indirect ELISA)

Specimen: Serum / CSF (Volume 1 ml)

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 laboratory before sending.

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

Method of payment

A. 1. Demand Draft in favour of 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 days (Maximum laboratory time) except for multiple sclerosis evaluation panel

Working hours 8.30 am to 5.30pm. Sunday holiday.

    2. Online / Internet Fund Transfer
        National Electronic Fund Transfer (NEFT)
        For format >> click here

B. Cash (to be paid at the Casualty Billing Counter at Amrita Hospital)

Address for sending Samples

Dr.Sudheeran Kannoth,
Neuroimmunology laboratory (T6F3)
Amrita Institute of Medical Sciences
Ponekkara PO 682041, or Elamakkara PO 682026
Kochi, Kerala,
India

Phone: +91 484 285 1234, 0484 6681234 Extension - 1356 & 6318
Mobile no: 09400998656 (Dr. Annamma Mathai-on call mobile)
Email: neuroimmunology@aims.amrita.edu

Publications Related to Neuroimmunology Laboratory

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.

Musk antibody

Sanders, Donald B., et al. "Clinical aspects of MuSK antibody positive seronegative MG." Neurology 60.12 (2003): 1978-1980.

Acetylcholine receptor antibody

Vincent, A., and J. Newsom-Davis. "Acetylcholine receptor antibody as a diagnostic test for myasthenia gravis: results in 153 validated cases and 2967 diagnostic assays." Journal of Neurology, Neurosurgery & Psychiatry 48.12 (1985): 1246-1252.

Ganglionic acetylcholine receptor antibody

Vernino, Steven, et al. "Autoantibodies to ganglionic acetylcholine receptors in autoimmune autonomic neuropathies." New England Journal of Medicine 343.12 (2000): 847-855.

Dopamine-2 receptor antibody

Dale, Russell C., et al. "Antibodies to surface dopamine-2 receptor in autoimmune movement and psychiatric disorders." Brain 135.11 (2012): 3453-3468.

MOG auto antibody

Reindl, Markus, et al. "The spectrum of MOG autoantibody-associated demyelinating diseases." Nature reviews neurology 9.8 (2013): 455-461.

VGKC antibody

Boronat, Anna, et al. "Encephalitis and antibodies to dipeptidyl‐peptidase–like protein‐6, a subunit of Kv4. 2 potassium channels." Annals of neurology 73.1 (2013): 120-128.

GFAP antibody

Flanagan, Eoin P., et al. "Glial fibrillary acidic protein immunoglobulin G as biomarker of autoimmune astrocytopathy: Analysis of 102 patients." Annals of neurology 81.2 (2017): 298-309.

Ganglioside antibody

Pestronk, A., et al. "A treatable multifocal motor neuropathy with antibodies to GM1 ganglioside." Annals of neurology 24.1 (1988): 73-78.

Willison, H. J., et al. "Miller Fisher syndrome is associated with serum antibodies to GQ1b ganglioside." Journal of Neurology, Neurosurgery & Psychiatry 56.2 (1993): 204-206.

Odaka, Masaaki, et al. "Bickerstaff’s brainstem encephalitis: clinical features of 62 cases and a subgroup associated with Guillain–Barré syndrome." Brain 126.10 (2003): 2279-2290.

GABA B receptor antibody

Lancaster, Eric, et al. "Antibodies to the GABA B receptor in limbic encephalitis with seizures: case series and characterisation of the antigen." The Lancet Neurology 9.1 (2010): 67-76.

AMPA receptor antibody

Lai, Meizan, et al. "AMPA receptor antibodies in limbic encephalitis alter synaptic receptor location." Annals of neurology 65.4 (2009): 424-434.

Multiple sclerosis evaluation – OCB detection

Hans Link,Yu-Min Huang:Oligoclonal bands in Multiple Sclerosis cerebrospinal fluid; An update on methodology and clinical usefulness. J Neuroimmunol, 2006;180;17-28

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 Laboratory