Melissa Cortez

Glucose intolerance, metabolic syndrome, and neuropathy

There is increasing evidence that impaired glucose tolerance (IGT) or metabolic syndrome may result in peripheral nerve injury, although the exact relationship between the conditions is still being characterized. There is animal model, epidemiologic, and clinical evidence to suggest a pathophysiologic relationship between neuropathy and metabolic syndrome, along with its components including obesity, dyslipidemia, and insulin resistance. IGT and metabolic syndrome are associated with subclinical nerve damage or are typically painful and sensory predominant, although autonomic involvement may also occur. Because there is often preferential small fiber injury and nerve conduction studies may be relatively insensitive, skin biopsy with assessment of intraepidermal nerve fiber density is often used to confirm the diagnosis. Treatment of metabolic syndrome and IGT-associated neuropathies should include diet and exercise counseling, maintenance of normoglycemia, and targeted pharmacologic therapy for modifiable risk factors. Further research is required to fully elucidate the complex pathophysiology, as well as identify optimal diagnostic and treatment approaches.

Autonomic symptom burden is associated with MS-related fatigue and quality of life

BACKGROUNDnNonspecific symptoms such as fatigue and dizziness are common in multiple sclerosis (MS), even in patients with normal exams. Little is known about the relationship of autonomic dysfunction with these symptoms and quality of life.nnnOBJECTIVEnAssess the association of autonomic symptom burden with fatigue, clinical status and quality of life.nnnMETHODSnSubjects completed an autonomic symptom (COMPASS-31), quality of life (MSQOL-54) and fatigue (FSS) questionnaire at their routine MS clinic follow-up. Demographic and clinical data were collected from the medical record. Pearson correlations were assessed between autonomic symptoms and fatigue, quality of life, disability and disease duration.nnnRESULTSnOne-hundred subjects completed the study (mean age 48 years; 78% female; 84% relapsing-remitting), mean disease duration was 14.7 years and mean EDSS 2.5. MSQOL-54 composite scores were 58 physical and 65 mental. COMPASS-31 correlated with MSQOL-54 (Physical R= -0.60; Mental -0.54; p<0.001) and FSS (R=0.51; p<0.001). There was no relationship between COMPASS-31 and EDSS (R=0, p=0.97) or disease duration (R= -0.02, p=0.84).nnnCONCLUSIONSnAutonomic symptom burden is correlated with decreased quality of life and increased fatigue. Autonomic symptoms are present early in the disease and at low disability and may reflect aspects of disease burden that are not well-captured by current disability measures.

Female hormonal exposures and neuromyelitis optica symptom onset in a multicenter study

Objective: To study the association between hormonal exposures and disease onset in a cohort of women with neuromyelitis optica spectrum disorder (NMOSD). Methods: Reproductive history and hormone use were assessed using a standardized reproductive survey administered to women with NMOSD (82% aquaporin-4 antibody positive) at 8 clinical centers. Using multivariable regression, we examined the association between reproductive exposures and age at first symptom onset (FS). Results: Among 217 respondents, the mean age at menarche was 12.8 years (SD 1.7). The mean number of pregnancies was 2.1 (SD 1.6), including 0.3 (SD 0.7) occurring after onset of NMOSD symptoms. In the 117 participants who were postmenopausal at the time of the questionnaire, 70% reported natural menopause (mean age: 48.9 years [SD 3.9]); fewer than 30% reported systemic hormone therapy (HT) use. Mean FS age was 40.1 years (SD 14.2). Ever-use of systemic hormonal contraceptives (HC) was marginally associated with earlier FS (39 vs 43 years, p = 0.05). Because HC use may decrease parity, when we included both variables in the model, the association between HC use and FS age became more significant (estimate = 2.7, p = 0.007). Among postmenopausal participants, 24% reported NMOSD onset within 2 years of (before or after) menopause. Among these participants, there was no association between age at menopause or HT use and age at NMOSD onset. Conclusions: Overall, age at NMOSD onset did not show a strong relationship with endogenous hormonal exposures. An earlier onset age did appear to be marginally associated with systemic HC exposure, an association that requires confirmation in future studies.

High risk of postpartum relapses in neuromyelitis optica spectrum disorder

Objective: To study the effect of pregnancy on the frequency of neuromyelitis optica spectrum disorder (NMOSD) relapse and evaluate rates of pregnancy-related complications in an international multicenter setting. Methods: We administered a standardized survey to 217 women with NMOSD from 7 medical centers and reviewed their medical records. We compared the annualized relapse rate (ARR) during a baseline period 2 years prior to a participants first pregnancy to that during pregnancy and to the 9 months postpartum. We also assessed pregnancy-related complications. Results: There were 46 informative pregnancies following symptom onset in 31 women with NMOSD. Compared to baseline (0.17), ARR was increased both during pregnancy (0.44; p = 0.035) and during the postpartum period (0.69; p = 0.009). The highest ARR occurred during the first 3 months postpartum (ARR 1.33). A total of 8 of 76 (10.5%) with onset of NMOSD prior to age 40 experienced their initial symptom during the 3 months postpartum, 2.9 times higher than expected. Conclusions: The postpartum period is a particularly high-risk time for initial presentation of NMOSD. In contrast to published observations in multiple sclerosis, in neuromyelitis optica, relapse rate during pregnancy was also increased, although to a lesser extent than after delivery.

Quantitative assessment of autonomic symptom burden in Postural tachycardia syndrome (POTS)

Postural tachycardia syndrome (PoTS) is a poorly understood disorder characterized by excessive tachycardia in the upright position. In addition, patients with PoTS often complain of non-postural symptoms, including fatigue, gastrointestinal and vasomotor fluctuations. The present study quantitatively assessed autonomic symptom burden in PoTS patients (n=32) using the COMPASS-31, compared to that of autonomic failure/neuropathy (AF/N; n=47) and asymptomatic, healthy controls (n=32). Using AIC model selection and regression analysis, we found differences in the contribution of individual COMPASS-31 domains, depending on the autonomic disorder. In PoTS, fatigue severity, orthostatic intolerance and pupillomotor symptom domains, contributed significantly to differences in COMPASS-31 scores compared to controls. In contrast, the secretomotor, gastrointestinal, bladder and vasomotor domains, contributed significantly to the AF/N model. Our results confirm an increase in autonomic symptoms across all functional domains in PoTS compared to controls, and with similar severity to AF/N, though with differing significant domain contributions. Our findings provide additional support that PoTS is indeed a syndrome of autonomic dysfunction beyond orthostatic intolerance, but also indicates the likelihood of disease-specific contributions to symptom burden, highlighting the need for application of expanded physiological assessment beyond orthostatic challenge, as well as disease-specific symptom assessment tools for use in PoTS.

Altered pupillary light response scales with disease severity in migrainous photophobia

Background Autonomic dysfunction and light sensitivity are core features of the migraine attack. Growing evidence also suggests changes in these parameters between attacks. Though sensory and autonomic responses likely interact, they have not been studied together across the spectrum of disease in migraine. Methods We performed digital infrared pupillometry while collecting interictal photophobia thresholds (PPT) in 36 migraineurs (14 episodic; 12 chronic; 10 probable) and 24 age and sex-matched non-headache controls. Quantitative pupillary light reflexes (PLR) were assessed in a subset of subjects, allowing distinction of sympathetic vs parasympathetic pupillary function. A structured questionnaire was used to ascertain migraine diagnosis, headache severity, and affective symptoms. Results Photophobia thresholds were significantly lower in migraineurs than controls, and were lowest in chronic migraine, consistent with a disease-related gradient. Lower PPT correlated with smaller dark-adapted pupil size and larger end pupil size at PPT, which corresponded to a reduced diameter change. On PLR testing, measures of both parasympathetic constriction and sympathetic re-dilation were reduced in migraineurs with clinically severe migraine. Conclusions In summary, we show that severity of photophobia in migraine scales with disease severity, in association with shifts in pupillary light responses. These alterations suggest centrally mediated autonomic adaptations to chronic light sensitivity.

International Issues: Expanding neurologic education to resource-poor countries Lessons from Moi Teaching Hospital

It is well-recognized that there is a disparity in health care resources and availability in low- and middle-income countries, often due to a combination of poverty, lack of clean water, inadequate nutrition, and political conflict. Yet it seems less attention is given to challenges specific to the provision of medical education in such developing nations. Besides war, famine, drought, and the AIDS epidemic, eastern African nations carry a heavy burden of neurologic disease1 and insufficient infectious disease programs,2 coupled with a paucity of subspecialty-trained providers. Over the past decade, there has been increasing concern over the so-called “brain drain”—the ongoing relocation of African doctors to more profitable parts of the world,3 presumably due to the challenges inherent to practicing in resource-limited settings. This is exemplified by the estimated 0.03 neurologists per 100,000 people in low-income African countries (compared to 1 to 10 per 100,000 in Western countries), and further by the lack of neurologists in all of sub-Saharan Africa.4 Similar estimates in sub-Saharan Africa suggest that there is only 1 neurosurgeon for every 4,000,000 people, with dedicated neurologic and neurosurgical services available in only a few private centers—institutions that are financially inaccessible to 90% of the population due to the nonexistence of health insurance systems.5

Quality of Life after Intra-arterial Therapy for Acute Ischemic Stroke

Few data exist about health-related quality of life outcomes after intra-arterial therapy (IAT) for acute ischemic stroke (AIS). We assessed stroke-specific quality of life (SS-QOL) in survivors of stroke after IAT. Consecutive patients undergoing IAT for AIS from 2005 to 2010 were retrospectively identified via an institutional database. SS-QOL (using the SS-QOL score) and disability status (modified Rankin Scale [mRS]) were prospectively assessed via mailed questionnaire. We analyzed quality of life (QOL) scores by domain and summary score, with a summary score of 4 or more defined as a good outcome. Analysis of variance (ANOVA) was used to model the effect of final recanalization status, stroke severity, and mRS on total QOL score. ANOVA and Pearson correlations were used to test the association between stroke severity/mRS and QOL/time since stroke, respectively. Of 99 patients with AIS, 61 responded, yielding 11 interim deaths, 7 incomplete surveys, and 43 complete surveys for analysis. Among responding survivors, overall QOL score was 3.9 (standard deviation 0.7); 77% of these reported good QOL. Scores were higher in recanalized patients in 11 of 12 domains but was significant only for mood. Although mRS was associated with stroke severity, QOL was independent of both. Seventy-seven percent of survivors of AIS who received IAT reported good QOL. Furthermore, these data suggest that SS-QOL is an independent outcome from stroke severity and disability status.

Patients With Migraine Have Substantial Reductions in Measures of Visual Quality of Life

Migraine is associated with several important visual symptoms, during both acute attacks and headache‐free intervals. The purpose of this investigation was to use validated vision‐related quality of life instruments to assess the effect of migraine on visual quality of life.