Dr. Simovic biography

Drasko Simovic, M.D. is a graduate of the University of Belgrade Medical School in Belgrade, Yugoslavia. He completed his internship at the Cabrini Medical Center, New York Medical College in New York, NY. He graduated from the Boston University Affiliated Residency Program in Neurology in Boston, MA, and completed two fellowships at St. Elizabeth’s Medical Center, Tufts University in Boston, MA. He is Board Certified in Neurology (ABPN), Electrodiagnostic Medicine (ABEM), Clinical Neurophysiology (ABPN-CN) and Disability Analysis (ABDA). He holds the academic appointment of Assistant Professor of Neurology at Tufts University, School of Medicine. His clinical and research interest includes ischemic and demyelinating polyneuropathies, electrodiagnostic evaluation of mononeuropathies, and gene therapy for neurological disorders.

Bibliography and research:

1. Weinberg DH, Simovic D : The terminal latency index in the carpal tunnel syndrome. Muscle and Nerve, 1996; 19: 1199; Presented at the 43^rd Annual Meeting, American Association of Electrodiagnostic Medicine, Minneapolis, MN; October 1996
2. Gorson CK, Allam G, Simovic D, Ropper AH: Improvement following Interferon alpha 2A in chronic inflammatory demyelinating polyneuropathy; Neurology, 1997; 48(3):777-780 Click for abstract

   Neurology 1997 Mar;48(3):777-80
   Improvement following interferon-alpha 2A in chronic inflammatory demyelinating polyneuropathy.

   Gorson KC, Allam G, Simovic D, Ropper AH.

   Neurology Service, St. Elizabeth's Medical Center, Boston, MA 02135, USA.

   Chronic inflammatory demyelinating polyneuropathy (CIDP) is a progressive or relapsing immune-mediated neuropathy usually responsive to plasma exchange, intravenous gammaglobulin or steroids, with some patients being refractory to these conventional therapies. We report a patient with CIDP who had spontaneous improvement after an episode of sepsis, but subsequently relapsed with severe generalized weakness; he was unresponsive to the conventional treatments for CIDP but had dramatic improvement following treatment with interferon-alpha 2A. Nerve conduction studies following treatment showed improved distal compound muscle action potential amplitudes without change in the degree of conduction block. The mechanism of action of interferon-alpha is unknown, but it may modulate proinflammatory cytokines that have a role in immune-mediated demyelination. Interferon-alpha may be an effective alternative therapy in patients with CIDP who relapse or are refractory to conventional treatments.

   PMID: 9065566 [PubMed - indexed for MEDLINE

3. Simovic D, Gorson CK, Ropper AH: Polyneuropathy associated with monoclonal gammopathy of undetermined significance (MGUS): comparison of IgM-MGUS and IgG-MGUS; Neurology, 1997; 48(3): A 52; Presented at the 49^th Annual Meeting, American Academy of Neurology, Boston, MA; April 1997
4. Gorson CK, Ropper AH, Simovic D, Allam G: Treatment of CIDP with Interferon alpha: A prospective open trial; Neurology, 1997; 48(3): A 87; Presented at the 49^th Annual Meeting, American Academy of Neurology, Boston, MA; April 1997
5. Acar D, Simovic D, Weinberg DH, Ropper AH: Mononeuritis multiplex mimicking acute demyelinating polyneuropathy; Presented at the Annual Stanley Cobb Assembly - Boston Society of Neurology and Psychiatry Meeting, Boston; April 1997
6. Simovic D, Weinberg DH: Terminal latency index in the carpal tunnel syndrome; Muscle and Nerve, 1997; 20: 1178-1180 Click for abstract

   Muscle Nerve 1997 Sep;20(9):1178-80
   Terminal latency index in the carpal tunnel syndrome.

   Simovic D, Weinberg DH.

   St. Elizabeth's Medical Center, Department of Neurology, Boston, MA 02135, USA.

   Our retrospective study assessed the validity of the median motor terminal latency index (m-TLI) in evaluation of carpal tunnel syndrome (CTS). In patients deemed most likely to have CTS, the mean m-TLI was markedly reduced at 0.25 while the controls had a mean m-TLI of 0.44. The m-TLI was abnormal in all of the "probable CTS" hands and in none of the control hands. The m-TLI is a sensitive adjunctive electrophysiologic measure for the presence of CTS.

   PMID: 9270676 [PubMed - indexed for MEDLINE]

7. Gorson CK, Ropper AH, Clark BD, Dew RB, Simovic D, Allam G: Treatment of chronic inflammatory demyelinating polyneuropathy with Interferon Alpha 2a; Neurology, 1998; 50: 84-87 Click for abstract

   Neurology 1998 Jan;50(1):84-7
   Treatment of chronic inflammatory demyelinating polyneuropathy with interferon-alpha 2a.

   Gorson KC, Ropper AH, Clark BD, Dew RB 3rd, Simovic D, Allam G.

   Division of Neurology, St. Elizabeth's Medical Center, Boston, MA 02135, USA.

   We performed an open-label, prospective, pilot study of interferon (IFN)-alpha 2a treatment for 6 weeks in 16 patients with chronic inflammatory demyelinating polyneuropathy (CIDP). All patients had failed to improve or relapsed after treatment with at least one conventional therapy (steroids, IV gamma globulin, or plasma exchange). Assessment included MRC strength score, leg sensory score, grip dynanometry, Rankin disability score, electrodiagnostic studies, and serum concentration of tumor necrosis factor-alpha. Nine (56%) improved after IFN-alpha therapy. Mean MRC score increased by 4.2 points (p = 0.01), and mean sensory score improved by 2.3 points (p = 0.02). Five patients improved five or more points on the MRC score, nine had slight improvement or were unchanged, and two worsened. We conclude that IFN-alpha may be effective in some patients with CIDP who relapse or fail to respond to conventional immunomodulating therapy.

   Publication Types:

   • Clinical Trial

   PMID: 9443462 [PubMed - indexed for MEDLINE]

8. Simovic D, Gorson CK, Ropper AH: Comparison of IgM-MGUS and IgG-MGUS polyneuropathy; Acta Neurologica Scandinavica,1998; 97: 194-200 Click for abstract

   Acta Neurol Scand 1998 Mar;97(3):194-200
   Comparison of IgM-MGUS and IgG-MGUS polyneuropathy.

   Simovic D, Gorson KC, Ropper AH.

   Neurology Service, St Elizabeth's Medical Center, Tufts University School of Medicine, Boston, MA 02135, USA.

   OBJECTIVE: To compare the clinical and electrodiagnostic features and response to treatment in patients with IgM-MGUS and IgG-MGUS associated polyneuropathy. MATERIAL AND METHODS: Retrospective review of 34 consecutive patients with MGUS associated neuropathy evaluated over 5 years. RESULTS: There were 19 patients with IgM-MGUS and 15 with IgG-MGUS. There were no differences in age, duration of symptoms, or distribution of motor and sensory symptoms or signs. IgM-MGUS patients had prolonged distal latencies of the median and ulnar motor potentials, greater slowing of the peroneal nerve conduction velocity and more often absent ulnar sensory potentials. Half of the patients in both groups improved following immunotherapy. CONCLUSION: IgM-MGUS patients had more severe demyelination on the nerve conduction studies, but there were no clinical features that differentiated the 2 groups. IgM and IgG-MGUS patients improved with plasma exchange and other immune therapies. Anti-MAG antibodies failed to distinguish a subgroup of patients with IgM-MGUS neuropathy.

   PMID: 9531437 [PubMed - indexed for MEDLINE]

9. Simovic D, Weinberg DH, Allam G, Hayes MT: A quantitative clinical scale for the carpal tunnel syndrome; Neurology, 1998; 50 (4): A302; Presented at the 50^th Annual Meeting, American Academy of Neurology, Minneapolis, MN; April 1998
10. Weinberg DH, Simovic D, Isner JM: Chronic ischemic monomelic neuropathy; Neurology, 1998;  50 (4):A207-208; Presented at the 50^th Annual Meeting, American Academy of Neurology, Minneapolis, MN; April 1998
11. Weinberg DH, Simovic D: Prospective study of the median nerve terminal latency index in carpal tunnel syndrome; Muscle and Nerve, 1998; 21 (11):1582; Presented at  the 45^th Annual Meeting, American Association of Electrodiagnostic Medicine, Orlando, FL; September 1998
12. Schratzberg P, Simovic D, Weinberg DH: Chronic ischemic neuropathy in peripheral arterial occlusive disease; Circulation, 1998; 98 (17) Supplement: I 268; Presented at the 71^st Scientific Session, American Heart Association, Dallas, TX; November 1998
13. Simovic D, Weinberg DH: The median nerve terminal latency index in diagnosis of carpal tunnel syndrome: a clinically based case selection study; Muscle and Nerve, 1999; 22:573-577 Click for abstract

    Muscle Nerve 1999 May;22(5):573-7
    The median nerve terminal latency index in carpal tunnel syndrome: a clinical case selection study.

    Simovic D, Weinberg DH.

    St. Elizabeth's Medical Center, Division of Neurology, Boston, Massachusetts 02135, USA.

    The terminal latency index (TLI) adjusts the distal motor latency (DL) for the terminal distance and the proximal nerve conduction velocity. We prospectively studied 66 patients in order to assess the sensitivity of the median nerve TLI for the diagnosis of carpal tunnel syndrome (CTS). Clinical and electrophysiological evaluations were completed by separate, blinded examiners. Based on the clinical diagnosis, 54 patients were judged to have CTS (CTS group) and 12 were believed not to have CTS. Control data were obtained from 38 healthy hands. The mean TLI was 0.26 +/- 0.04 in the CTS group and 0.43 +/- 0.04 in the control group (P < 0.001). The sensitivity of the TLI was 81.5%. The TLI was statistically better than the median motor DL and sensory peak latency (PL) to the second digit. The TLI was always abnormal when the median mixed-nerve palmar latency was abnormal. In three cases from the CTS group, the TLI was the only abnormal electrophysiological parameter. The median TLI is a useful, sensitive electrodiagnostic parameter for CTS.

    Publication Types:

    • Clinical Trial

    PMID: 10331355 [PubMed - indexed for MEDLINE]

14. Simovic D, Ropper AH, Weinberg DH: Improvement in ischemic limb neuropathy after vascular endothelial growth factor gene therapy; Annals of Neurology, 1999; 46 (3): 463; Presented at the 124 ^th Annual Meeting, American Neurological Association; Seattle, WA; October 1999
15. Simovic D, Ropper AH, Isner JM, Weinberg DH: Improvement in ischemic limb neuropathy after VEGF gene transfer; Circulation, 1999; Supplement I, 100 (18): I-770; Presented at the 72^nd Scientific Session, American Heart Association; Atlanta, GA; November 1999
16. Simovic D, Weinberg DH: Carpal tunnel syndrome; Archives of Neurology, 2000; 57:754-755 Click for abstract

    Arch Neurol 2000 May;57(5):754-5
    Carpal tunnel syndrome.

    Simovic D, Weinberg DH.

    Division of Neurology, St Elizabeth's Medical Center, Tufts University School of Medicine, Boston, Mass, USA.

    Carpal tunnel syndrome (CTS) is the most frequently encountered mononeuropathy in the clinical practice. Although now a well recognized entity, it took almost 100 years from the initial observations until the pathophysiology of the disorder was finally accepted as a median nerve compression at the wrist.

    Sir James Paget (1854)1 was the first to describe the clinical features of CTS. In his first case, a man developed pain and impaired sensation in the hand from the trauma of a cord drawn tightly around his wrist. In his second case, a tardy median nerve palsy was a consequence of a distal radius fracture. This patient improved with wrist immobilization and thus was also the first description of treatment with a neutral wrist splint , a method still in use today. Three decades later James Putnam (1880)2 presented a clinical series of 37 patients with "... disturbances of a subjective sensibility of the skin, giving rise to what is popularly known as numbness recurring periodically, coming on especially at night ... in some cases simply letting the arm hang out of the bed or shaking it about for some moments would drive the numbness away…J.Putnam 1880 “ 2. This vivid description of CTS is quite remarkable considering it was one of the initial clinical observations and that it occurred at the end of the 19th century.

    Publication Types:

    • Historical Article

    PMID: 10815148 [PubMed - indexed for MEDLINE]

17. Simovic D, Isner JM, Ropper AH, Pieczek A, Weinberg DH: Improvement in chronic ischemic neuropathy following intramuscular phVEGF₁₆₅ gene transfer in patients with critical limb ischemia; Archives of Neurology, 2001; 58 (5):761-768 Click for abstract

    Arch Neurol 2001 May;58(5):761-8
    Improvement in chronic ischemic neuropathy after intramuscular phVEGF165 gene transfer in patients with critical limb ischemia.

    Simovic D, Isner JM, Ropper AH, Pieczek A, Weinberg DH.

    St Elizabeth's Medical Center, 736 Cambridge St, Boston, MA 02135, USA.

    OBJECTIVE: To investigate the effects of vascular endothelial growth factor gene therapy on ischemic neuropathy in patients with critical limb ischemia. DESIGN: An open-label, dose-escalating trial. Patients with angiographically proven critical leg ischemia received injections of phVEGF(165) human plasmid in the muscles of the ischemic limb. Testing before treatment and at 3 and 6 months included (1) symptom severity score, (2) clinical examination score, and (3) electrophysiologic studies. Clinical and electrophysiologic examiners were masked to each other's findings. SETTING: A tertiary care referral hospital and a major teaching affiliate of Tufts University School of Medicine, Boston, Mass. RESULTS: Of 29 consecutive patients enrolled, 17 (19 limbs) completed the 6 months of study. Six patients had diabetes. Compared with baseline studies, treated patients had significant clinical improvements in the symptom score (P<.01), sensory examination score (P<.01), total examination score (P =.01), peroneal motor amplitude (P =.03), and quantitative vibration threshold (P =.04). Improvement in the vascular ankle-brachial index in treated legs (P<.01) corresponded to improvement in neuropathy in the same limb. Neurologic improvement was seen in 4 of 6 patients with diabetes who completed the study. No clinical, electrophysiologic, or vascular improvements were observed in untreated legs. CONCLUSIONS: Ischemic neuropathy might be a reversible condition, and therapeutic angiogenesis might be an effective treatment. The presence of diabetes does not preclude a response to this therapy.

    PMID: 11346371 [PubMed - indexed for MEDLINE]

18. Weinberg DH, Simovic D, Isner JM, Ropper AH: Chronic ischemic monomelic neuropathy from critical limb ischemia; Neurology, 2001; 57(6): 1008-1012 Click for abstract

    Neurology 2001 Sep 25;57(6):1008-12
    Chronic ischemic monomelic neuropathy from critical limb ischemia.

    Weinberg DH, Simovic D, Isner J, Ropper AH.

    Department of Neurology, Tufts University School of Medicine, St. Elizabeth's Medical Center, Boston, MA 02135, USA. David.Weinberg.MD@cchcs.org

    OBJECTIVE: To describe the peripheral neuropathy resulting from chronic and critical arterial leg ischemia. METHODS: The authors evaluated 19 patients on entry to a gene therapy treatment trial for chronic and critical leg ischemia. Measurements included medical history, examination, neurologic symptom (NSS) and neurologic examination (NES) scores, motor and sensory nerve conduction studies, and quantitative sensory testing. The critically ischemic leg was compared with the less affected contralateral limb. RESULTS: All patients experienced pain from skin ulceration or vascular claudication, but many also had rest pain (58%), numbness (58%), burning (42%), and paresthesias (37%) in the ischemic foot that were consistent with peripheral nerve ischemia. Only three patients (16%) were free of neuropathic symptoms. The most common asymmetric neurologic signs included hypalgesia (74%), toe weakness (64%), hyperesthesia (63%), and pallanesthesia (53%) in the distal leg. NSS and NES were more abnormal in the critically ischemic leg, as were distal motor, total motor, and sensory examination subscores (p < 0.01 for each). Sural sensory potentials were reduced or absent, frequently on both sides. The symptomatic limb had reduced tibial motor amplitudes and increased thermal (cold) sensory thresholds (p < 0.01 for both) whereas the distal latencies, conduction velocities, and vibration thresholds were similar in the two legs. CONCLUSIONS: There is a predominantly sensory neuropathy associated with chronic and critical limb ischemia. Neuropathic symptoms are often obscured by the effects of ischemia on other tissues. The neurophysiologic changes suggest that the underlying pathophysiology is a distal axonopathy affecting nerve fibers of all sizes. Measures of blood flow in the leg correlate with neurologic symptom scores, examination scores, and electrophysiologic testing

    PMID: 11571325 [PubMed - indexed for MEDLINE]

19. Simovic D: Autoimmune neuropathies and treatment with intravenous immunoglobulins; Therapy, 2005, 2 (5),797-805 Click for abstract

    Therapy 2005 Sep 2 (5):797-805
    Autoimmune neuropathies and treatment with intravenous immunoglobulins.

    Simovic D

    Department of Neurology, Tufts University School of Medicine, St. Elizabeth's Medical Center, Boston, MA 02135, USA. info@emglaboratory.com

    Intravenous immunoglobulins (IVIg) are an effective treatment for a variety of immune mediated neuropathies. The benefits have been recognized from the controlled studies for Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN). In monoclonal gammopathy of undetermined significance (MGUS) and neuropathy the effectiveness is variable. Tolerability of IVIg is very good and the adverse reactions are usually minor. Further controlled trails are needed to assess the efficacy of second IVIg infusion in non responders in GBS, maintenance IVIg dose and frequency in CIDP and MMN, efficacy of IVIg in diabetes associated CIDP and the benefits of combination therapy with other immunomodulating medications.

20. Ropper AH, Gorson CK, Gooch CL, Weinberg DH, Pieczek A, Ware JH, Kershen J, Simovic D, Schratzberger P, Kirchmair R, Losordo D: VEGF Gene Transfer for Diabetic Polyneuropathy: A Randomized Double Blinded Trial; Ann Neurol. 2009 Apr;65(4):386-93
    Click for abstract

    Ann Neurol. 2009 Apr;65(4):386-93
    Vascular endothelial growth factor gene transfer for diabetic polyneuropathy: a randomized, double-blinded trial.

    Ropper AH, Gorson KC, Gooch CL, Weinberg DH, Pieczek A, Ware JH, Kershen J, Rogers A, Simovic D, Schratzberger P, Kirchmair R, Losordo D.

    Department of Neurology, Brigham and Women's Hospital, Boston, MA 02115, USA. aropper@partners.org

    OBJECTIVE: Randomized, blinded trial of intramuscular gene transfer using plasmid vascular endothelial growth factor (VEGF) to treat diabetic polyneuropathy. METHODS: Diabetic patients with polyneuropathy were randomized to receive a VEGF-to-placebo ratio of 3:1. Three sets of injections were given at eight standardized sites adjacent to the sciatic, peroneal, and tibial nerves of one leg. Primary outcomes were change in symptom score at 6 months and a prespecified overall clinical and electrophysiological improvement score. Secondary outcomes were differences in symptoms, examination scores, visual analog pain scale, nerve conduction, and quantitative sensory testing. RESULTS: Thirty-nine patients received plasmid VEGF and 11 received placebo. Mean symptom score improved in both legs at 6 months, favoring VEGF over placebo (-1.2 +/- 0.5 vs -0.9 +/- 0.5; p < 0.01 after adjustment for change in the untreated leg) and compared with the untreated leg (-0.7 +/- 0.5; p = 0.02). The region of sensory loss and visual analog pain scale improved in the treated group (-1.5 vs -0.5; p = 0.01). Twelve of 39 VEGF versus 2 of 11 placebo patients met criterion for overall improvement. Other measures including nerve conduction potentials did not improve. There were 84 adverse events in VEGF patients, and 22 were serious; there were 51 events in placebo patients, and 2 were serious. INTERPRETATION: Intramuscular plasmid VEGF gene transfer improved diabetic neuropathic symptoms, meeting primary end-point criteria for efficacy but not affecting most secondary measures. Treatment was associated with more serious adverse events that did not reach statistical significance. These results are not conclusive but may justify further clinical study.

    PMID: 19399887 [PubMed - indexed for MEDLINE]

RESEARCH PROJECTS:

• A prospective neurological and electrodiagnostic study of patients undergoing gene therapy for critical peripheral vascular disease
• Clinical and neurophysiological evaluation of patients undergoing revascularization of the lower extremities: A prospective study
• Repetitive stimulation test of the phrenic nerve using a diaphragmatic wire recording electrode: A new diagnostic technique
• Development of an animal model for the ischemic monomelic polyneuropathy and evaluation of the effect of VEGF (Vascular Endothelial Growth Factor) on peripheral nerve regeneration in laboratory animals
• A prospective clinical and neurophysiological evaluation of patients with ischemic polyneuropathy