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Year : 2022  |  Volume : 65  |  Issue : 5  |  Page : 230-232
Current status of neuromuscular pathology: An overview with special reference to Indian Scenario

1 Department of Pathology, Nizam's Institute of Medical Sciences, Hyderabad, Telangana, India
2 Department of Neuropathology, NIMHANS, Bengaluru, Karnataka, India
3 Department of Pathology, AIIIMS, New Delhi, India

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Date of Web Publication11-May-2022

How to cite this article:
Uppin M, Mahadevan A, Sarkar C. Current status of neuromuscular pathology: An overview with special reference to Indian Scenario. Indian J Pathol Microbiol 2022;65, Suppl S1:230-2

How to cite this URL:
Uppin M, Mahadevan A, Sarkar C. Current status of neuromuscular pathology: An overview with special reference to Indian Scenario. Indian J Pathol Microbiol [serial online] 2022 [cited 2022 Jun 30];65, Suppl S1:230-2. Available from: https://www.ijpmonline.org/text.asp?2022/65/5/230/345065

Neuromuscular pathology is perhaps a less attractive field with very few takers among the pathology trainees and juniors. This could be remotely related to the fact that majority of neuromuscular disorders (NMDs) remain incurable and processing of muscle and nerve biopsies requires a specialized set up, different from a routine histopathology lab. The number of neuromuscular labs in India are limited and many states share a single such facility. However, these rare disorders are being acknowledged with novel diagnostic methodologies and therapeutics in the form of gene therapy. The examples of Duchenne muscular dystrophy and spinal muscular atrophy have embarked the potential value of gene therapy.[1],[2] The government is taking initiatives at national level on rare diseases which includes NMDs. In this direction, consortia for NMDs have been proposed to explore cheaper diagnostic and therapeutic options for the benefit of patients. All this will not be possible without an accurate diagnosis which is the fundamental responsibility of a neuromuscular lab.

Clinical examination, genetics, auto antibodies, and biopsy evaluation form the pillars of diagnostic strategy in hereditary and acquired NMDs. The review articles in this section have emphasized each of these aspects in detail using diagnostic algorithms, tables, and illustrations, which will help the readers in understanding the seemingly unexplored world of NMDs with much ease.

Last couple of decades have brought in advances in molecular genetics of inherited NMDs including muscular dystrophies, congenital, and metabolic myopathies.[3] With the wider availability and awareness of genetics, this is being preferred as the initial diagnostic tool over invasive biopsy techniques. It has become imperative to understand the role of genetics in diagnosis particularly in prenatal testing and counselling, which is important for family planning. There are varieties of platforms available for genetic testing which need to be used judiciously for the cost-effective benefit to the patients. The review articles on some of these inherited NMDs address the finer nuances of the genetics in elaborate detail including the methodology, utility, and limitations.

Inflammatory myopathy (IM) is a large group of potentially treatable muscle diseases. Muscle specific and associated auto antibodies are emerging as robust serologic means of diagnosis.[4],[5] The antibodies are unique to the subtypes of IM with respect to the clinical features, course of the disease, and prognosis. Majority of the laboratories have adopted the testing of these antibodies by an immunoblot method for a rapid and noninvasive diagnosis of IM. The review on the auto antibodies deals with the entire spectrum of clinico serologic classification of IM.

So what is left for pathology and why is there a need for establishing a neuromuscular lab would be an obvious question in the reader's mind. Many of the NMDs were first described after the biopsy findings and are named after their pathologic description till date. The clinical features are not characteristic in every patient. Moreover, the findings can be overlapping between various inherited NMDs as well as acquired disorders. The initial genetic testing need not yield a positive result and may show “variants of unknown significance.” These problems are often encountered in routine practice when the clinician seeks the help of a biopsy. As for the IM, about 30% of them are sero negative and can be false negative by initial blot. The more specific immunoprecipitation techniques are difficult to establish and still remain unavailable in resource limited settings. These remain as justifiable indications for pathology-based diagnosis of IM.

Establishing a neuromuscular lab require dedicated efforts since it requires stringent and specific working conditions with different processing apart from that used for routine histopathology laboratory. It is important to follow an order in choosing a site for muscle biopsy, its transport to the lab, and immediate cryoprocessing. The interpretation of muscle biopsies rests on various enzyme histochemical stains (EHC), immunohistochemistry (IHC), immunoblot, and electron microscopy. Obtaining of tissues/biopsies for standardization of these techniques is not easy, and I am sure every diagnostic neuromuscular expert in the country has stories to share on their experience of starting and running a lab. The review article on the basic requirements for establishing the lab will make the efforts sound a little easier and more methodical for the benefit of the readers.

Muscle biopsy findings have been an important part of all the evolving classification schemas on IM.[6] The biopsy criteria are well defined in every subtype of IM, and it is necessary to understand the contribution of muscle biopsy in diagnosis of IM. The review article on this aspect introduces readers to the strength and limitations of muscle biopsy in IM highlighting the EHC and IHC used for diagnosis. The biopsy findings vary with different autoantibodies, which explain the pathogenic differences in these subtypes.

The various EHCs and special stains demonstrate many structural abnormalities in the muscle fibers. These structural changes help in delineation of congenital, metabolic, and mitochondrial abnormalities. The pathologists need to be aware of the exhaustive range of EHC and special stains in biopsy for appropriate diagnosis. Also, many myopathies still are named after their pathologic descriptions, particularly the subtypes of congenital myopathies.[7] The clinical presentation of certain metabolic myopathies can be acute when biopsy with EHC and special stains can give early and rapid diagnosis compared to the genetic testing, which takes longer time. All these important aspects of biopsy diagnosis have been covered in the respective reviews. The illustrations are exemplary and would be a visual treat to the readers. Photographic memory is a large part of learning pathology, and these articles would help to create the same in myopathology.

Many immunohistochemical markers can be performed on cryosections for confirming the subtypes of dystrophies as well as IM. Newer IHCs like MxA have shown high specificity for diagnosis of dermatomyositis. The pattern and analysis of the available IHC have been highlighted in the various reviews.

A few of the myopathies remain uncharacterized by routine EHCs, in which cases ultrastructural studies can be of immense help. Electron microscopy needs a special attention with respect to processing and interpretation, which has been elaborately dealt with in a separate review article. This article helps in reemphasizing the role of EM through some breathtaking illustrations to make the reader understand that it is not a dying art.

As is true for myopathology, the pathology of nerve biopsies also remains less explored, read, and understood. The low diagnostic yield perhaps makes this seemingly invasive technique less popular among pathologists. We try to break these negative notions about nerve biopsy interpretation through four important reviews that explain the technique and utility of nerve biopsies to arrive at a final diagnosis.

The burden of leprosy in India is high and diagnosis poses a challenge owing to varying clinical manifestations, morphologic spectrum, and unculturable causative Lepra bacillus.[8] The review article gives an exhaustive overview of all the available tests for the diagnosis of leprosy, which range from morphology to molecular studies.

Immune inflammatory neuropathies are potentially treatable acquired neuropathies that have characteristic clinical and pathologic features. Recent advances in antibodies have revolutionized the diagnosis of these neuropathies for the benefit of the patients. It is important to understand these updates which form important noninvasive and early diagnosis of inflammatory neuropathies, which has been well elaborated in the review.

Hereditary neuropathies are a large group that needs attention due to shift of diagnosis from pathology to genetic testing. The significance of biopsy is emphasized when the clinical manifestations are uncharacteristic and also to pick up an acquired cause which makes the underlying inherited condition manifest.

The role of skin punch biopsy in evaluation of small fiber neuropathies has been established over the last three decades.[9] However, this remains a largely unexplored pathology in India owing to cumbersome technical specifications and lack of proper Indian controls. The review article gives a detailed overview by the experts in the field including techniques, processing, and interpretation.

All the review articles have been written by expert national and international faculty (Dr Liza Rajsekhar, Dr Madhu Nagappa, Dr Prajnya Ranganath, Dr Hans-Hilmer Goebel, Dr Gayathri Narayanappa, Dr Yasha T C, Dr Anita Mahadevan, Dr Kiranpreet Malhotra, and Dr Nandeesh BN along with all the co-authors) with large experience in the respective fields. The readers will surely enjoy the academic feast that has been provided through these articles. If this section of the special issue helps in shedding the fear of neuromuscular pathology, with more postgraduates opting to explore this field, shall serve the purpose of these efforts.

In the [Table 1], we have tried to provide the details of existing neuromuscular labs in the country and sincerely wish that these numbers rise in the coming few years.
Table 1. List of Neuromuscular laboratories in India

Click here to view

To conclude, this issue is one of its kinds which includes experts reviews all aspects of neuropathology and thus will serve as a handy textbook for the students of pathology, neurology, neurosurgery, and many other specialities. Apart from the esteemed author panel, the articles have been reviewed by well known and senior faculty in the field of neurosciences. We would like to sincerely acknowledge their efforts without which this issue would be impossible.

   References Top

Scoto M, Finkel R, Mercuri E, Muntoni F. Genetic therapies for inherited neuromuscular disorders. Lancet Child Adolesc Health 2018;2:600-9.  Back to cited text no. 1
Ryan MM. Gene therapy for neuromuscular disorders: Prospects and ethics. Arch Dis Child 2021:archdischild-2020-320908. doi: 10.1136/archdischild-2020-320908.  Back to cited text no. 2
Laing NG. Genetics of neuromuscular disorders. Crit Rev Clin Lab Sci 2012;49:33-48.  Back to cited text no. 3
Khadilkar SV, Dhamne MC. What is new in idiopathic inflammatory myopathies: Mechanisms and therapies. Ann Indian Acad Neurol 2020;23:458-67.  Back to cited text no. 4
  [Full text]  
Benveniste O, Goebel HH, Stenzel W. Biomarkers in inflammatory myopathies-An expanded definition. Front Neurol 2019;10:554.  Back to cited text no. 5
Tanboon J, Uruha A, Stenzel W, Nishino I. Where are we moving in the classification of idiopathic inflammatory myopathies? Curr Opinion Neurol 2020;33:590-3.  Back to cited text no. 6
North KN, Wang CH, Clarke N, Jungbluth H, Vainzof M, Dowling JJ, et al. Approach to the diagnosis of congenital myopathies. Neuromuscul Disord 2014;24:97-116.  Back to cited text no. 7
Sengupta U. Elimination of leprosy in India. Indian J Dermatol Venereol Leprol 2018;84:131-6.  Back to cited text no. 8
[PUBMED]  [Full text]  
Lauria G, Lombardi R. Skin biopsy: A new tool for diagnosing peripheral neuropathy. BMJ 2007;334:1159-62.  Back to cited text no. 9

Correspondence Address:
Megha Uppin
Additional Professor, Department of Pathology, Nizam's Institiute of Medical Sciences, Hyderabad, Telangana
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0377-4929.345065

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