Multiple Sclerosis Fellowship

Tehran University of Medical Sciences

School of Medicine

Department of Neurology

 

 

FELLOWSHIP PROGRAM IN MULTIPLE SCLEROSIS

Introduction

 

Multiple Sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system that usually affects young and middle-aged adults and causes a considerable social and economic burden. During recent years MS has become one of the most common reasons for admissions to a neurological ward. Now MS is recognized throughout the world, with around 2.5 million affected individuals. Although the disease was recognized in the 19th century, there were limited data on the diagnosis, pathophysiology, and management of MS for the last 50 years. With every step of progress in immunology, imaging and biotechnology, there was indeed progress in our understanding of etiology and diagnosis of this potentially disabling disease. Even with such an amazing progress in technology, the exact etiology and absolute cure for MS is not known yet; thus, MS has been the focus of interest in clinical and basic science research in the past decades. Hundreds of MS research groups, centers and clinics are conducting research on this field ranging from animal studies to human clinical trials. Due to their interests and efforts, MS has become a partially treatable disease with the introduction of the drugs that are able to reduce annual relapse rates and delay disability.

 

MS management starts with diagnosis and continues with strategies to control relapses, increasing quality of life of the patients, symptomatic treatments and rehabilitation. With our progress in this field, management of different patients has become more complicated and in some cases needs special training. These facts led the pioneer MS research centers around the world to start special MS training programs for neurologists for better management and addressing of the ever-growing issues about understanding, diagnosis and treatment of Multiple Sclerosis.  The moderate to high prevalence of MS in Iran (20-50 in 100,000) has led the local neurologist to pay special attention to patient management and research. Tehran University of Medical Sciences, as the leading medical university in Iran provides 18 months of advanced training in diagnosis, treatment and clinical research in Multiple Sclerosis. This Fellowship program is conducted under the supervision of neurologists specialized in MS atTehran University of Medical Sciences and the invited authorities from other countries.

 

TEHRAN UNIVERSITY OF MEDICAL SCIENCES MS CENTERS

 

Sina MS Centre was founded in 2007 in Sina University Hospital, the oldest hospital in Tehran. It is located in downtown Tehran and provides care for more than 2,000 registered patients from all over the country, 1,100 of whom are visited regularly in the outpatient clinic. Under the direction of Dr. Mohammad Ali Sahraian, this centre provides comprehensive care including diagnostic and second opinion consultation for ambulatory patients, hospitalization for seriously ill patients, and rehabilitative care, apart from clinical and basic research and teaching. Currently, 15 research projects are ongoing to investigate the effect of some experimental treatments as well as the etiological and epidemiologic aspects of MS. The staff consists of two neurologists with interest and experience in MS, two research assistant physicians, three MS-trained nurses, one physiotherapist, and one psychiatrist. The Centre is also closely linked to the Radiology and Pathology departments. A lab with three different areas of staff is affiliated with the Centre, providing a gene bank for MS patients.  In addition, the Neurology Department which trains 12 neurology residents and medical students communicates frequently with the MS Centre.

 

Imam Khomeini’s MS Center

 

Imam Khomeini Hospital is the biggest hospital affiliated with Tehran University of Medical Sciences and is located in the central part of Tehran. The Department of Neurology is one of the oldest departments having been involved in the training of neurology residents for more than 60 years. The Iranian Center for Neurological Research is located in this hospital and MS research group is headed by Prof. Mohammad Hossien Harirchian. More than 600 Patients are registered in Imam Khomeini MS center and receive ambulatory and inpatient care.

A molecular lab is affiliated to this center and is involved in research and molecular investigations on MS. MS clinics are active for 2 days per week.  A lab for performing evoked potentials is available in this department as well. An equipped imaging center in Imam Khomeini Hospital with 3 tesla MRI and facilities for fMRI and MRS are in close cooperation with the MS Center.  Several research projects on demyelinative disorders have been conducted in Imam Khomeini MS Center and currently 2 RCTs as well as 5 investigations about MRS in PPMS, and immunopathogenesis and genetic aspects of MS are ongoing in this center. There is also a cooperative genetic research program between Imam Khomeini MS center and St George’s University of London.
 

Faculty Members

 

1.       Professor  Amir Reza AZIMI; MD, Neurologist, Assistant Professor of Neurology, Tehran University of Medical Sciences

2.       Professor Mohammad Reza HADIAN; PhD,  Professor of Rehabilitation, Tehran University of Medical Sciences

3.       Professor Mohammad Hossien HARIRCHIAN; MD, Neurologist, Chair of Neurology Department, Tehran University of Medical Sciences

4.       Professor  Sanaz Ahmadi KARVIGH; MD, Neurologist

5.       Professor Jamshid LOTFI; MD, Emeritus Professor of Tehran University of Medical Sciences, President of the Iranian MS Society

6.       Professor Alireza MINAGAR; Invited Lecturer, Professor of Neurology, Louisiana State University Health Science Center, Shreveport,   USA

7.       Professor Abdulmohammad ROSTAMI; Invited Lecturer, Chair of Department of Neurology, Thomas Jefferson University Hospital, USA

8.       Professor Farinaz SAFAVI; MD, PhD, Invited Lecturer,  Thomas Jefferson University, USA

9.       Professor Mohammad Ali SAHRAIAN; MD; Neurologist, MS Fellowship, Head of Advisory Board of the Iranian MS Society

10.     Professor Mansoureh TOGHA; MD, Neurologist, Professor of Neurology, Tehran University of Medical Sciences

 

 

DESCRIPTION OF THE FELLOWSHIP PROGRAM

 

Clinical Research Fellowship in Multiple Sclerosis

 

In this 18-month program, fellows would receive comprehensive training in the clinical evaluation and management of the patient with MS and related disorders in both adult and pediatric populations. Fellows will also have the opportunity to participate in a wide variety of original clinical research projects involving all aspects of MS. Fellows are encouraged to design original projects that relate to their interests. There is a special focus on Neuroradiology and MRI-based research and training. It is our intent to produce clinically and academically well-trained individuals who will be able to contribute in advancing the state of knowledge of Multiple Sclerosis and improving the care given to the MS patients. We will take honor in supporting our trainees academically and personally as they begin their careers as MS specialists. Given that most clinical trials in MS have an MRI component as an outcome measure, considerable effort and time of an MS-specialized neurologist is devoted to the analysis of the MRI scans of the patients. Intensive individual training is offered in this program by our neuroradiologist and neurologist with special expertise in Multiple Sclerosis. Our program is designed for those applicants who do not have the license to practice medicine in Iran. It will provide the fellows with the opportunity to fully master their ability to use MRI as a diagnostic tool as well as an outcome measure in the evaluation of the therapeutic interventions in MS.  In addition, the fellows will participate in research programs and become skilled in the MRI based research, mainly conventional MRI techniques.

 

 

1.             CURRICULUM

 

1.1.         Patient Care and Management

 

The fellows will receive comprehensive training in the clinical evaluation, diagnosis and follow-up of the MS patient and related disorders (e.g. neuromyelitisoptica, neurosarcoid, CNS vasculitis, transverse myelitis, CRION and clinically isolated syndrome). They will gain experience in varied treatment approaches and understand different rationales in managing patients with acute exacerbation or unresponsiveness to standard treatments. The fellows will be responsible for visiting the patients in the outpatient MS clinic and the in-patient MS ward according to the designated schedule. They will be supervised directly at all times by one of the faculty members in the Multiple Sclerosis Division.

 

1.2.         Weekly Conferences

 

The weekly neurology conference allows fellows to learn more about problem cases and management of the referral patients from all over the country and discuss the most recent research findings with their colleagues.

 

1.3          Research

 

Fellows are expected to take part in the enrollment, follow-up and data interpretation of the currently ongoing trials. Supervised, independent or joint research is encouraged during the fellowship training. In addition, The Department of Epidemiology and Statistics at Tehran University of Medical sciences offers a number of courses in epidemiology, biostatistics, and design and conduct of clinical trials which can help the fellows promote their research skills. The scientific writing courses are available and the fellows will be offered the assistance in the preparation and submission of articles for publication in peer-reviewed journals.

 

2.             Requirements

 

The applicants for the clinical Multiple sclerosis fellowship must have satisfactorily completed an accredited Neurology Residency. A letter of reference is also required. Invited applicants are interviewed by the program director. Having a prior training in research methods is preferred but not mandatory.

 

 

3.             Educational Goals and Objectives 

 

At the end of the program Fellows will be able to:

• Gain profound insight into the cause and mechanisms of multiple sclerosis and related inflammatory demyelinating disorders (neuromyelitisoptica, clinically isolated syndrome)
• Diagnose the patients with different types of MS and other related disorders. (neuromyelitisoptica, neurosarcoid, CNS vasculitis, Susac’s, transverse myelitis) and rule out other differential diagnoses.
• Interpretation of MRI and other relevant imaging outcomes.
• Acquire the knowledge of utilizing the currently available diagnostic tools (serology, CSF analysis,…) and their clinical and prognostic implication.
• Select the appropriate and individual-based choice of disease modifying therapy for relapsing-remitting MS patients. (interferons, glatiramer acetate, natalizumab, fingolimode,…)
• Recognize the existing unconventional and alternative therapies and novel undertrial drugs.
• Become skilled in the treatment of progressive or aggressive MS, including the use of chemotherapeutic, combination therapies, rescue treatments and other innovative agents.
• Manage pain, spasticity, fatigue, bowel-, bladder- or sexual dysfunction, mood disorders and etc with proper symptomatic treatment and control relapses.
• Identify and manage the potential adverse effects of the medications.
• Distinguish unresponsiveness to a prescribed treatment and decide for a proper substitution strategy.
• Offer suitable rehabilitation program for the chronic neurologic illness.
• Learn the logistics of working within a multi-disciplinary team.
• Gain experience in the use and interpretation of clinical outcome measures such as the EDSS score, the multiple sclerosis functional composite score, nine-hole peg test and paced auditory serial addition test (PASAT).
• Design and Conduct Clinical Trials and interpret the findings and accomplish qualified publication.

 

TOPICS AND SUBTOPICS

 

1. Genetics & Epidemiology

 

· Provide a summary of current epidemiologic facts about MS.

~ Geography

~ North-South gradient

~ Clusters, epidemics

~ Incidence and prevalence

~ Migration studies

~ Racial/ethnic distribution

 

· Describe the genetics of MS, from population studies to molecular mechanisms.

~ HLA associated loci

~ Risk related to affected family member

~ Twin studies

~ Molecular sites of genetic contribution to susceptibility (TCR, MHC expression, immunoglobulin)

~ Emerging data on the proteomic profiles of MS lesions

 

· Provide information regarding gender bias in MS.

~ Sex ratio

~ Differences in disease severity between sexes

~ Effects of pregnancy, menses, and menopause breast feeding

 

· Discuss possible roles of stress and trauma and infection in etiology of MS

 

· Vitamin D

 

· Smoking

 

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2. Neurophysiology

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· Discuss electrical transmission in normal nerves.

~ Architecture of normal myelinated nerves

~ Generation of action potentials

~ Saltatory conduction

 

· Describe disorders of conduction in demyelinated nerves.

~ Decreased conduction velocity, conduction block, temporal dispersion

~ Ephaptic transmission

~ Heat sensitivity

~ Ion channel distribution

 

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3. Neuroimmunology

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~ Describe normal mechanisms for immune reactivity and self-tolerance

~ Describe possible mechanisms for loss of self-tolerance (Autoimmunity)

~ List possible candidates for “MS antigen” ( e.g., MBP, MOG)

~ Discuss role of infections in etiology of MS

~ Describe role of cytokines in MS

~ Describe role of adhesion molecules in MS

~ Discuss T cell biology

~ Role of other immune cells (Glial, B cells…)

~ Describe the role of the blood brain barrier in MS and trafficking of lymphocytes into the CNS

 

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4. Neuropathology

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· Present gross pathologic and histologic findings associated with MS lesions.

~ Inflammation, edema, demyelination, gliosis, axonal transection

~ Distribution of plaques in the CNS

~ Histologic differences between acute and chronic plaques

~ Immunocytochemistry of the MS lesion

~ Lassman/Luchinetti subtypes

 

· Describe mechanisms of oligodendrocyte and myelin damage in MS.

~ Antibody/ compliment mediated

~ Cell mediate

~ Role of T cell, astrocytes, macrophages

~ Cytokines

~ Chemokines

 

· Discuss possible mechanisms of axonal damage in MS.

 

· Discuss potential mechanisms of remyelination

 

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5. Diagnosis

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· List diagnostic criteria for diagnosis of MS

~ Schumacher

~ Poser, Paty, Scheinberg

~ Mc Donald (2001,revised 2005, 2010)

 

· Generate differential diagnosis of MS in several categories

 

· Other autoimmune( e.g., collagen vascular)

~ Sjogren’s

~ SLE

~ RA

~ Behcet’s

~ Undifferentiated connective tissue syndromes

~ Overlap syndromes

~ Neurosarcoidosis

 

· Infectious

~ HIV

~ HAART associated HIV myelopathy

~ Lyme

~ HTLV-1

~ Neurosyphilis and treponemal diseases

 

· Vascular

~ Vasculitis

~ ANCA associated vasculitides

~ CADASIL

~ Binswanger’s

~ Antiphospholipid Syndrome (APS)

~ Susac’s Syndrome

~ Embolic disease

~ Hypertensive disease

 

· Hereditodegenerative

~ Spinocerebellar ataxias and trinucleotide repeat disorders

~ Multiple Systems Atrophy, cerebellar type (MSA-C)

~ OPCA

~ Metachromatic leukodystrophy

~ Adrenoleukodystrophy

~ Hereditary ataxias including Friedrich’s ataxia

~ Mitochondrial diseases

 

· Neoplastic

~ Brainstem glioma

 

· Structural

~ ACM

~ Syrinx

~ Structural myelopathy ( tumor or disc)

~ Primary brain tumor

 

· Toxic/metabolic

~ B 12 deficiency

~ Cigeratoa intoxication

~ Nitrous oxide toxicity syndrome

~ Vitamin E deficiency

~ Copper deficiency

 

· MS variants

~ Balo’s

~ Schilders

~ Marburg

~ NeuromyelitisOptica (NMO)

~ Diagnostic criteria

~ Role of aquaporin-4 antibody

~ Treatment options

~ Opticospinal MS and NMO spectrum disorders

 

· Describe sensitivities and specificities of paraclinical tests

~ MRI

~ Indications for specific MR sequences

~ Evoked potentials

~ Cerebrospinal fluid

~ Electrophoretic and isoeletric focusing technologies for CSF analysis

 

· Discuss indications for each testing modality

 

· List appropriate tests to exclude diagnosis of MS ( e.g. collagen vascular serologies)

 

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6. Clinical Skills

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· Discuss natural history including different temporal and clinical courses

~ CIS

~ R/R

~ SP

~ PP

~ PR

~ Mild

 

· Evidence for immunologic differences between above

 

· Present guidelines for defining prognosis

~ Prognostic indicators

~ Age

~ Gender

~ Race

 

· Type of initial symptoms

 

· Interval to next attack

 

· Degree of recovery from attack

 

· Disease subtype

 

· Statistics recumulative disability years after diagnosis

 

· Role of MRI in formulating prognosis and monitoring disease activity

 

· Outcome measures

~ EDSS

~ MSFC

~ OCT

~ MRD

~ Quality of life scales

 

· Describe common and uncommon symptoms in MS

~ Visual

~ Motor

~ Sensory/pain syndromes

~ Genitourinary

~ Cerebellar

~ Brainstem

~ Cognitive

~ Fatigue

 

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7. Prophylactic Management

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· Present results from clinical trials of FDA approved immunomodulatory drugs

~ Beta-interferon 1b

~ Glatiramer acetate

~ Mitoxantrone

~ Natalizumab

~ Fingolimod

 

· Off label medications and immunotherapies

 

· Emerging immunotherapies; oral, MAb, other

 

· Discuss guidelines for initiation and maintenance of therapy

 

· List common side effects (and their management) for each of the above agents

 

· Plasma Exchange

 

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8. Symptomatic Management

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· Discuss treatment of acute exacerbations

~ Steroid regimens

~ IVIG

~ Plasmapheresis

 

· Rehabilitative modalities

 

· Pseudo-exacerbations

~ Treat underlying precipitant, e.g., infection

 

· Present primary symptoms and discuss their management

 

· Algorithm for diagnosis of bladder dysfunction

 

· Genitourinary-Bowel

 

· Sexual dysfunction ( male)

~ Normal male anatomy and innervations

~ Physiology of normal sexual response

~ Impotence/erectile dysfunction

 

· Fatigue

 

· Tremor/Ataxia

 

· Visual

 

· Psychological/Cognitive

 

· Immobility complications

~ Wound care

~ Contractures

~ Relieve spasticity

~ Maximize mobility

~ Botox

~ Surgical remediation

~ Aspiration

~ Osteoporosis

 

· Describe tertiary symptoms and treatment approaches

~ Social/ Familial issues

~ Marital difficulties

~ Parenting issues

~ Role changes

~ Financial hardship

~ Vocational

Interested international students need to complete and submit our online application form

 

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