Leticia Tornes

Clinical Expression of Multiple Sclerosis in Hispanic Whites of Primarily Caribbean Ancestry

Objective: The clinical characteristics of multiple sclerosis (MS) are not well defined in Hispanic populations. We hypothesized that disease presentation in Hispanic white (HW) patients will be different from non-Hispanic white (NHW) patients given their ancestral background and reported lower disease prevalence. This study was undertaken to compare HW of primarily Caribbean ancestry to NHW on clinical characteristics of MS. Methods: We assessed 312 HW and 312 NHW patients with definite MS for clinical disease characteristics obtained through consented review of medical records. In order to assess the relationship between age-related phenotypes and ethnicity, linear regression was used. Logistic regression was used to assess the relationship between ethnicity and descriptors of disease presentation and severity as well as presence of neurological symptoms. Results: We observed a significantly younger age at diagnosis (p = 1.38E-02) and age at exam (p = 2.36E-05) in HW. However, age at first symptom did not differ significantly between the two groups. Furthermore, within HW, the mean age at first symptom and age at diagnosis was significantly younger in those born in the United States (p < 1.00E-03 for both). Interestingly, we noted an increase in ambulatory disability in HW patients, primarily among those with relapsing disease (p = 4.18E-03). Conclusions: We found several differences in age-related phenotypes and disease severity between HW of primarily Caribbean origin and NHW patients. To our knowledge, this is the largest study to date that examined the clinical characteristics of MS in Hispanic patients of largely Caribbean origin.

Multiple Sclerosis and the Cerebellum

Multiple sclerosis (MS) is an inflammatory, demyelinating disease that has unpredictable symptomatology and severity. Cerebellar manifestations in MS can be present at any time of the clinical course. Early cerebellar findings are a predictor of disability and disease progression. Most patients have cerebellar manifestations once they enter the progressive stages of the disease. Of the cerebellar findings, tremor is by far the most common.

Multiple Sclerosis and the Spinal Cord

Many clinical manifestations of multiple sclerosis (MS) may be attributed to spinal cord disease. MS may have classic presentation or a more complex presentation. MS is mainly a relapsing remitting disease, but there is also an insidious form that is progressive, known as primary progressive MS (PPMS). PPMS may not be identified for extended periods of time and should be on the differential of chronic myelopathies. Early diagnosis of MS rests on awareness of a clinically isolated syndrome and the required magnetic resonance imaging criteria. Early diagnosis results in early institution of treatment and a superior response.

NMO spectrum presenting as partial myelitis

Sir, A 38-year-old right-handed African American woman presented in August 2011 to the emergency room with 2 weeks of progressive ascending numbness to below her abdomen. The patient reported no difficulty with ambulation, changes in urination or bowel movements, blurry vision or double vision. Her neurological exam revealed a thoracic (T10) sensory level to pinprick, decreased vibratory and proprioceptive sensation in both lower extremities, and hyperreflexia in the lower extremities. Magnetic resonance imaging (MRI) of the spinal cord showed a T2 hyperintense lesion associated with cord edema at T5–T6 that enhanced with gadolinium (Figure 1A). The remainder of the spinal cord was normal. Brain MRI revealed nonspecific bilateral subcortical frontal white matter T2 hyperintense lesions (Figure 1B). Serology including vitamin B12, methylmalonic acid, angiotensin converting enzyme, and serum protein electrophoresis were normal. Antinuclear antibody was weakly positive at 1:40. Antibodies to hepatitis A, B, and C, anti-Ro/ssa and ant-La/ssb, HTLV I/II, and Lyme disease were not detected. Cerebrospinal fluid (CSF) revealed 14 white blood cells, 1 red blood cell, normal protein and glucose, no oligoclonal bands, normal IgG index and cytology. CSF VDRL was negative. CSF polymerase chain reaction for Epstein–Barr virus, herpes simplex virus, cytomegalovirus, varicella zoster virus, and enterovirus were negative. The patient received intravenous methylprednisolone 1 g/day for 5 days with significant improvement in her neuropathic pain. She was placed on gabapentin for further symptomatic management. Serum and CSF NMO-IgG antibody tests were pending at the time of discharge. Six weeks later, the patient presented with severe allodynia from the breasts downward. Her exam revealed decreased strength in the right lower extremity, 4+/5 proximally and 2/5 distally. Laboratory tests were reviewed from her prior admission. CSF NMO-IgG antibody was negative, but serum NMO-IgG antibody was positive. MRI of her spinal cord revealed a longitudinally extensive T2 hyperintense lesion throughout her spinal cord from C2 to T7 (Figure 1C) with gadolinium enhancement from C5 to T7. The patient was again treated with intravenous methylprednisolone 1 g/day for 5 days with significant improvement in her weakness and allodynia. She was diagnosed with neuromyelitis optica spectrum disorder (NMOSD) and initially placed on oral prednisone and azathioprine, but developed nausea, diarrhea, and elevated liver transaminases. She was subsequently treated with rituximab (two 1 g infusions at a 2-week interval) which she tolerated well. There are few reported cases in which NMOSD presents initially as acute partial transverse myelitis (APTM).1,2 A retrospective review of 22 cases of APTM by Scott et al.1 found only one case that was seropositive for the NMOIgG antibody. Although we do not advocate testing every patient with APTM for the NMO-IgG antibody, we do recommend close monitoring of these patients, as a minority will, in fact, develop NMO or NMOSD. This is clinically important as patients with NMO or NMOSD that are positive for the NMO-IgG antibody are at high risk for relapse3,4 and should be treated with immunosuppressants to prevent future attacks.

Focal segmental glomerulosclerosis secondary to subcutaneous interferon β-1a treatment in a patient with multiple sclerosis

Interferon (IFN)-β is a first line treatment for patients with relapsing remitting multiple sclerosis (RRMS) that has been shown to decrease relapse rates, reduce magnetic resonance imaging (MRI) disease burden and possibly delay onset of disability (Arnason, 2005). There are few reports of nephrotic syndrome related to Minimal Change Disease (MCD) or Focal Segmental Glomerulosclerosis (FSGS) during treatment with IFN-α (Nishimura et al., 2002; Tola et al., 2003; Rettmar et al., 1995). There are fewer reports of nephrotic syndrome induced by IFN-β (Tola et al., 2003; Auty and Saleh, 2005; Kumasaka et al., 2006). We report a 41 year old African American woman with RRMS that developed FSGS after 3 months of treatment with IFN-β-1a 3 times weekly and review the previously published cases.

Native ancestry is associated with optic neuritis and age of onset in hispanics with multiple sclerosis

Hispanics with multiple sclerosis (MS) present younger and more often with optic neuritis (ON) as compared to Whites in the western United States. Regional differences related to Hispanic genetic admixture could be responsible. We investigated the association between global genetic ancestry and ON and age at onset of MS in Hispanics.

HSV-2 encephalitis presenting as multifocal ischemic stroke

OBJECTIVE To report a rare case of HSV-2 meningoencephalitis presenting as multifocal ischemic stroke. BACKGROUND While most ischemic strokes are treated with antithrombotics (or anticoagulants) and aggressive vascular risk factor management, a high index of suspicion needs to be maintained to identify those cerebral infarcts requiring alternate treatments. Recognizing infectious causes of stroke is of particular importance, as treatment is effective if readily instituted. CASE SUMMARY The patient is a 68-year-old right-handed Hispanic female with a medical history of systemic lupus erythematosus on immunosuppressive therapy, hypertension, and migraine, who initially presented with a slight holocephalic headache of 3 weeks followed by acute left-sided numbness in the setting of urine tract infection. She also experienced brief hallucinations, attributed initially metabolic causes. She was treated for ischemic stroke, after MRI showed three areas of acute ischemia on DWI, involving the right anterior inferior insula and two regions in the right frontal cortex. Three days later she developed transient slurring of speech and right-sided facial weakness that resolved within an hour. MRI did not show any new findings suggestive of acute stroke. A lumbar puncture was then performed which showed significantly elevated proteins and white count with 100[percnt] lymphocytes predominance. PCR was positive for HSV type 2 in CSF and she was started on acyclovir 800 mg IV every 8 hours for a three week course. The patient continued to do well with improvement in her headaches and remained otherwise symptom free and neurologically intact. CONCLUSION A high index of suspicion needs to be maintained to diagnose infectious vasculitis. A history of immunosuppression and headache preceding cerebral infarction were important factors that ultimately led to the appropriate work up and diagnosis in this case. Lumbar puncture and prompt initiation of antiviral treatment is essential in stroke case of suspected CNS infection with HSV-2. Disclosure: Dr. Zhang has nothing to disclose. Dr. Sumida has nothing to disclose. Dr. Margolesky has nothing to disclose. Dr. Tornes has nothing to disclose. Dr. Ramos has nothing to disclose. Dr. Koch has nothing to disclose.

Neuroleptic Malignant Syndrome Associated with Refractory Acute Disseminated Encephalomyelitis

We present the case of a young man who was transferred to our hospital with worsening acute disseminated encephalomyelitis (ADEM) despite treatment with intravenous methylprednisolone, intravenous immunoglobulin and plasma exchange. He developed neuroleptic malignant syndrome (NMS) without the use of dopamine-modulating drugs. His progressive clinical improvement started after treatment with intravenous cyclophosphamide and methylprednisolone. In our patient, acute demyelination with severe bilateral inflammation of the basal ganglia could have caused a state of central dopamine depletion, creating proper conditions for the development of NMS. Significant clinical improvement of our case after treatment with intravenous cyclophosphamide and steroids provides further evidence for a possible role of the inflammatory lesions in the pathogenesis of NMS in association with ADEM.

Contents Vol. 44, 2015

A. Anand, Chandigarh G.B.J. Anderson, Chicago, Ill. A. Barber, Auckland S. Barker-Collo, Auckland D.A. Bennett, Chicago, Ill. F. Bermejo, Madrid N.E. Bharucha, Mumbai G. Boysen, Copenhagen M. Brainin, Krems C. Brayne, Cambridge M.M.B. Breteler, Bonn A. Culebras, Syracuse, N.Y. R. D’Alessandro, Bologna J.F. Dartigues, Bordeaux J.L. Fisher, Columbus, Ohio G.M. Franklin, Seattle, Wash. M. Giroud, Dijon A.J. Hannan, Melbourne, Vic. G. Hankey, Perth, W.A. W.A. Hauser, New York, N.Y. M.A. Ikram, Rotterdam J. Kesselring, Valens C. Ketzoian, Montevideo S.J. Kittner, Baltimore, Md. Y. Kokubo, Osaka A. Korczyn, Tel-Aviv J.F. Kurtzke, Falls Church, Va. S.-M. Lai, Kansas City, Kans. L. Liu, Beijing M. Liu, Chengdu E.D. Louis, New Haven, Conn. S. Mehan, Sirsa M.M. Mehndiratta, New Delhi K. Nakashima, Yonago L. Nelson, Stanford, Calif. P.G. Parmar, Auckland P.-M. Preux, Limoges A.H. Rajput, Saskatoon, Sask. K. Rockwood, Halifax, N.S. P.M. Rothwell, Oxford R.L. Sacco, Miami, Fla. O. Shafey, Abu Dhabi Y. Shinohara, Tokyo W.F. Stewart, Danville, Pa. A. Thrift, Melbourne, Vic. T. Truelsen, Copenhagen C. Tzourio, Paris N. Venketasubramanian, Singapore H. von Holst, Stockholm W. Wang, Beijing International Association of Neurology and Epidemiology (IANE)

Transverse myelitis presenting in a patient with Hughes-Stovin syndrome

Hughes-Stovin syndrome (HSS) is a lymphocytic vasculitis defined by the constellation of venous thrombosis and multiple pulmonary artery aneurysms. Aneurysmal rupture with massive hemorrhage is a frequent fatal event. HSS is thought of as a forme fruste of Behcets disease (BD), sharing similar histological findings, but without other associated manifestations that characterize BD. Classically patients with HSS do not have oral and genital ulcers, inflammatory eye disease, skin pathergy, nor do they develop neurological manifestations that can arise with