Hereditary Neuromuscular disorders in Pakistan are common due to consanguineous marriages-Dr.Sara Khan


 Neurology Update 2016 proceedings

Hereditary Neuromuscular disorders in Pakistan
are common due to consanguineous
marriages - Dr.Sara Khan

Muscle pathology plays a central role in diagnosis hence Centralization
of Muscle Biopsy Service is important - Prof. I. Nishino

KARACHI: Dr. Alam along with Dr. Mamoona Siddiqui chaired the session devoted to Genetic testing and Genetic disorders during the recently concluded 16th Neurology Update 2016 organized by Pakistan Society of Neurology in collaboration with Pakistan Stroke Society, Pakistan Headache Society, Movement Disorders Society of Pakistan and Neurology Awareness and Research Foundation here from December 22-25, 2016.  Dr. Sara Khan from Aga Khan University was the first speaker whose presentation was on Current and future trends for Neuro Muscular Medicine in Pakistan. She also talked about the Asian Oceania Myology Center which was established in January 2001.  Prof. Nonaka is the President.  Its objectives are to promote research in neuromuscular field in member countries. It provides educational opportunities for young researchers. It also encourages and strengthens multidisciplinary collaboration.

Speaking about the human resource in neurology in Pakistan, Dr. Sara Khan said that at present we have one hundred sixty trained neurologists for a population of over two hundred million. We have nineteen foreign trained while the other are trained in Pakistan.  Two of them are trained in neuromuscular medicine.  In Pakistan consanguineous marriages is quite common which account for about 61.2% of marriages. Hereditary neuromuscular disorders are very high. Some of the challenges we face Include non-availability of clinical expertise, delay in referrals diagnostic testing.  The diagnostic testing challenges include lack of know how regarding how to prepare biopsy slides which is difficult and Lack of training in reading these slides. Neurologists rely more on clinical impressions rather than these slides. Then there is lack of availability of genetic testing. Other issues she talked about were delay in seeking specialized care, anger, frustration, doctor shopping and if prognosis of hereditary disorders is explained, society does not accept the diagnosis.  They do not wish to go for tests as it costs money and then there is Lack of follow up.  When clinical features become more obvious it helps physicians to make better diagnosis, she remarked.

Speaking about future trends Dr.Sara Khan said that we have all sort of neuromuscular disorders. We need to invest in pathologists they should go and get formal training in neuromuscular disorders. We have had some facilities for genetic testing. With Muscle MRI radiologists will help if inflammatory process is going on or it is a hereditary disorder.  These patients can be used for research sponsored by pharmaceutical companies. For stroke interventional neurology is being practiced. Drugs are now available for multiple sclerosis, diagnostic tests are also available. One should examine these patients and give them some hope, she added.

Prof I. Nishino from Japan talked about basic approach to muscular disorders. These diseases, he said are classified by pathological features. He pointed out that almost 70% of muscle biopsies are diagnosed at their center and during the Year 2016, they had looked at 912 biopsies. Centralization of such a service, he pointed out, is the key. Muscle biopsy center should be a centralized service. We do genetic analysis for which we do need muscle biopsy as many diseases are classified by pathological features. He was of the view that all muscle diseases will be redefined in the days to come. We need both geno typing and phenol typing.   Talking about Grower’s signs, he mentioned difficulty in extending hip joint. He showed video   of a patient suffering from Duchene muscular dystrophy (DMD) and said that now these patients live longer but previously they used to die at the average age of twenty years.  Now we have some patients who are in their 60s. Exxon 51 skipping therapy has now been approved by FDA. He then discussed the management of three cases. POMPE disease, he said, is now treatable. His next patient was of Necrotizing Myopathies. During October 2010 to December 2014, they had 460 cases of Myositis of which 37% were INNM cases.  Statins, he said, was an important risk factor but it is not always the case. He also referred to idiopathic inflammatory myopathies.  With correct diagnosis one can help the patients suffering from rapidly progressive anti   HMGCR myopathies.  He then discussed the case of a 39 years old female with head drop. Muscle biopsy was done and this showed to be a case of Sporadic Late Onset Myopathy (SLONM). Nemaline Myopathy is mostly acquired. He concluded his presentation by stating that muscle pathology plays a central role in diagnosis. Muscle imaging, Genetic diagnosis are necessary for therapy and now treatable muscle diseases are increasing.

In the next session Prof. Nonaka from Japan talked about Major Congenital Myopathies based on pathological findings. He pointed out that Nemaline Myopathy account for   26%, Congenital Fiber type Disproportions 17% and infantile myotubular Myopathy 13%.  Congenital Myopathy shares a common pattern of clinical features i.e. Floppy infant. Classification includes paralytic form and non-paralytic form.  There is facial muscle involvement. He then showed some slides of congenital myotonic dystrophy, central core disease, and preferential neck muscle weakness. Nemaline Myopathy disease is usually progressive. Funnel chest is commonly seen in Nemaline Myopathy.  Gene mutations in Nemaline Myopathy he said, needs to be discovered. He also referred to central core disease in Nemaline Myopathy. Facial muscle involvement might cause mutation in Lamina A/C Gene congenital laminopathy.  Cardiac check up is important in such patients to avoid sudden cardiac death.

Dr. T. Umapathi spoke on Peripheral Neuropathy. He pointed out that these patients complain of numbness and weakness. Speaking about clinical approach to weakness he said that these patients present with distal weakness, glove and stocking pattern. Try to find out the cause of this neuropathy?  This neuropathy could be because of diabetes? He also talked about distal symmetrical polyneuropathy, dermopathy as denervation of skin is common in diabetes mellitus. Those patients with diabetes who have long duration of disease and poor control will develop peripheral neuropathy. Retinopathy and Neuropathy should go hand in hand. There can be bilateral severe foot drop. Vagus nerve gets affected first. One can see heart rate variability. The patient he was discussing, he said, also had cardiomypathy as well. Amyloid neuropathy was the cause of his neuropathy. It is a treatable condition. He also discussed about treatment induced neuropathic diseases. TIND can occur with the use of Insulin, Diabetologists should be careful about it. They should look for distinct features like burning, sensation, itching in young hypertensive patients. Some patients may have rash in Scrotum, angiokeratoma and this cannot be diagnosed unless one examines the patients carefully. This emphasizes the importance of detailed history and physical examination.

Vaculitic neuropathy has typical clinical features. It is also a treatable condition. Treatment consists of removal of antigen, control of infection, pain relief, splintage and these patients will also require immunosuppression. He then talked about Gullian Barrie Syndrome,  and also referred to AMAN axonal Degeneration.  The patient he discussed had the diagnosis of CDIP. He warned that corticosteroids are sharp knife, use them with care. Make sure patient should not develop complications. Screen infection. One can avoid complications with healthy diet and physical activity.  One should give steroids in such a way that you avoid complications. He then also talked about Focal CIDP. CISP- Chronic Immune Sensory Polyradioculopathy is also treatable.  Pathophysiology of AMAN was also discussed and described in detail besides clinical approach to a weak patient with unusual form of CIDP. Managed properly, the patient was eventually cured. He concluded his presentation by stating that some of these diseases are not so treatable but we should not give up. Let us keep some hope for these patients. During the discussion it was pointed out that we do need to have facilities for muscle biopsy to diagnose and treat these rare diseases.

Prof. Akhtar Sherin along with Col. Babar chaired the next session. Dr.Nadir Ali Syed was the main speaker in this session who talked about Dystonia.  It was defined as a movement disorder with sustained muscle contractions often agonistic muscle, repetitive twisting movements with abnormal postures. He discussed in detail how to distinguish them from other myoclonus disorders.  What work up needs to be done and how to treat these patients? He pointed out that until a few years ago these patients were sent to psychiatrists for management. He further stated that these patients themselves know the tricks which they do and the dystonia goes away.  Sometimes it is action specific, if the patients start walking backward, dystonia goes away.  He also referred to writer’s cramps and musicians’ cramps. These patients have inconsistent movements. These symptoms have abrupt onset. He also talked about incongruous movements, deliberate slowness crying out voluntary movement, spontaneous remission. MRI in these patients is often normal. They have hyper excitability,  using some music instrument lead to brain changes which leads to dystonia.

Continuing Dr. Nadir Ali said that it may start from leg and then spread to the whole body. He also showed some examples of dystonia of tongue and focal dystonia. Most dystonia, he stated begin as focal Dystonias and most start in childhood. Writer’s cramp can occur in 40s and 70s. It can be focal and multifocal. In generalized type Trunk and two other sites are involved. If more than one part is involved it can be segmental if one or two regions are involved and hemidystonia if half the body is involved. DYT1, Dr. Nadir Ali Syed stated is more common, it has early onset and starts around ten years of age. Medications are helpful in early states. DYT5 is seen in young patients. It also has early onset and is very common in females. DYT11 has onset in late first or second decade of life. It is also known as heredodegenerative dystonia.  To evaluate these patients, he referred to Levodopa trial in DYT1 and DYT6. While managing these patients with family history of dystonia, review the medications, prescribed and those which these patients may be taking at their own without any prescription. All patients with Hemidystonia should have MRI of Brain. Some of these patients could have it related to Valporic Acid and once you stop this drug, patient becomes better. Treat underlying neurological disorder and use sensory tricks. Anti cholinergic is the first drug of choice and if there is no response, add Benzodiazepines. If nothing works, refer these patients for DBS. All children with dystonia should have a trial with Levodopa. Anti epileptic drugs are also quite effective.  He then talked about the contra indications to Botulium Toxin which includes previous allergic reaction, motor nervous disease, pregnancy, use of aminoglycosides, Myasthenia Gravis, infection at the proposed injection site.  Surgical options include Deep Brain Stimulation and intrathecal baclofen.  During the discussion it was pointed out that patients with Down’s syndrome and Rett’s Syndrome can have seizures.