Pseudo-anticipation in Creutzfeldt-Jakob disease is due to a rhomboid-shaped artifact.

BACKGROUND AND PURPOSE: Previous studies have reported conflicting results regarding possible anticipation in familial E200K Creutzfeldt-Jakob disease (fCJD). Our objective was to use a large database to assess the age of disease onset (AODO) in CJD. METHODS: The study population included 477 CJD patients [266 with fCJD, 145 with sporadic CJD (sCJD) and 66 patients of Libyan origin but negative family history] from the Israeli registry of CJD conducted since 1954. In all patients, AODO in relatives and family trees was documented. Comparison of AODO was done using a paired t test and regression using Pearson correlation for birth and year of onset. RESULTS: The initial analysis in 52/73 families in which more than one generation was affected revealed an AODO of 63.30 ± 9.44 in the first generation compared to 56.96 ± 8.99 in the second generation (P < 0.001). However, inspection of individual AODO values plotted by year of birth showed a clear rhomboid methodological artifact generated by missing data of many young onset CJD patients who died before the database began to function in 1954 and of many late onset CJD patients missing at the present time since they will only develop the disease in the future. The 'generation' effect completely disappears if analysis is performed by year of disease onset or for the periods in which complete data are available. CONCLUSIONS: In this very large dataset, true anticipation in fCJD patients was not detected. It is plausible that previous reports supporting the presence of anticipation are biased by a rhomboid-shaped data availability artifact.

Clinical and radiological determinants of transient symptoms associated with infarction (TSI).

BACKGROUND: The definition of transient ischemic attack was traditionally based on clinical features only. The wide use of magnetic resonance imaging (MRI) led to the definition of a new entity - transient symptoms associated with infarction (TSI). It is unclear why patients with similar radiological infarctions may have different clinical manifestation - ranging from complete symptoms resolution to major neurological sequelae. We sought to determine which factors differentiate acute diffuse weighted imaging (DWI) lesion presentation - stroke versus TSI. METHODS: 282 Participants, recruited for the Tel-Aviv Brain Acute Stroke Cohort study (TABASCO), were enrolled consecutively. Participants underwent extensive cognitive evaluation, wide laboratory tests and brain MRI scans evaluated for cerebral small vessel disease (SVD) biomarkers, according to the STRIVE protocol. Demographic and clinical characteristics were also examined. RESULTS: A total of 239 patients had stroke and 43 patients had TSI. TSI patients had smaller average lesion volume (0.77 cm3 versus 2.64 cm3, p = 0.002). Lesion location did not differentiate TSI and stroke. Stroke patients had elevated inflammatory markers, unrelated to lesion size (CRP 4.2 mg/L versus 1.7 mg/L, p = 0.011). TSI patients had better global cognitive score and MoCA score at admission and 24 months following the index event (p < 0.001). TSI patients also had better Berg balance score (p = 0.004). No significant association was found with MRI SVD markers. CONCLUSIONS: Lesion size, but not location, differentiates TSI and stroke, especially at a cutoff value of 10 cm3. Elevated inflammatory response was linked to worse course independently of lesion volume. Cognitive and high function tests are associated to the clinical phenotype of ischemic lesion and may be a marker of brain reserve and compensatory abilities. SVD markers do not differ between TSI and stroke patients and probably do not fully capture the extent of brain vascular pathology and reserve.

High hair cortisol concentrations predict worse cognitive outcome after stroke: Results from the TABASCO prospective cohort study.

BACKGROUND AND PURPOSE: The role of stress-related endocrine dysregulation in the development of cognitive changes following a stroke needs further elucidation. We explored this issue in a longitudinal study on stroke survivors using hair cortisol concentrations (HCC), a measure of integrated long-term cortisol levels. METHODS: Participants were consecutive cognitively intact first-ever mild-moderate ischemic stroke/transient ischemic attack (TIA) survivors from the Tel Aviv Brain Acute Stroke Cohort (TABASCO) study. They underwent 3T magnetic resonance imaging (MRI) scanning and were cognitively assessed at admission, and at 6, 12 and 24 months post-stroke. Scalp hair samples were obtained during the initial hospitalization. RESULTS: Full data on baseline HCC, MRI scans and 2 years neuropsychological assessments were available for 65 patients. Higher HCC were significantly associated with a larger lesion volume and with worse cognitive results 6, 12 and 24 months post-stroke on most of the neurocognitive tests. 15.4% of the participants went on to develop clinically significant cognitive decline in the follow-up period, and higher HCC at baseline were found to be a significant risk factor for this decline, after adjustment for age, gender, body mass index and APOE e4 carrier status (HR=6.553, p=0.038). CONCLUSIONS: Our findings suggest that individuals with higher HCC, which probably reflect higher long-term cortisol release, are prone to develop cognitive decline following an acute stroke or TIA.

Gait instability in valproate-treated patients: Call to measure ammonia levels.

OBJECTIVE: Hyperammonemia induced by valproate (VPA) treatment may lead to several neurological and systemic symptoms as well as to seizure exacerbation. Gait instability and recurrent falls are rarely mentioned as symptoms, especially not as predominant ones. METHODS: We report five adult patients with frontal lobe epilepsy (FLE) who were treated with VPA and in whom a primary adverse effect was unstable gait and falls. RESULTS: There were four males and one female patients with FLE, 25-42-year-old, three following epilepsy surgery. All of them were treated with antiepileptic drug polytherapy. Gait instability with falls was one of the principal sequelae of the treatment. Patients also exhibited mild encephalopathy (all patients) and flapping tremor (three patients) that developed following the addition of VPA (three patients) and with chronic VPA treatment (two patients). VPA levels were within the reference range. Serum ammonia levels were significantly elevated (291-407 µmole/L, normal 20-85) with normal or slightly elevated liver enzymes. VPA dose reduction or discontinuation led to the return of ammonia levels to normal and resolution of the clinical symptoms, including seizures, which disappeared in two patients and either decreased in frequency or became shorter in duration in the other three. CONCLUSIONS: Gait instability due to hyperammonemia and VPA treatment is probably under-recognized in many patients. It can develop when the VPA levels are within the reference range and with normal or slightly elevated liver enzymes.

Quality-of-life perception by Parkinson's disease patients and caregivers.

BACKGROUND: The quality-of-life (QoL) perception by Parkinson's disease (PD) patients and their caregivers (CG) has not been studied in depth. OBJECTIVE: To examine patient/proxy agreements on the PD QoL Questionnaire (PDQ-39), the Scale of Quality of Life of Care-Givers (SQLC) and the Multidimensional Caregiver Strain Index (MCSI). METHODS: Patients with PD and their CG completed the above-mentioned questionnaires about themselves and each other. The intraclass correlations between their scores (paired t test) were compared. RESULTS: Twelve patient-CG pairs were studied. Agreements for QoL items were strong and comparable for the total scores of the PDQ-39, SQLC and MCSI questionnaires (75.4% ± 14%; 78.1% ± 14.1% and 78.2% ± 14.3%, respectively). Agreements ranged from moderate to strong (0.57-0.88, P≤.05) for the patients' physical condition (PDQ-39 items 3, 5, 6, 8, 12-15, 23, 24, 35), mental concentration (item 31) and depression (item 17). Disagreements were apparent in 20%-25% of the pairs and were particularly significant for PDQ-39 items #33 and #25 (embarrassment of patients in public and distressing dreams or hallucinations), in which the CG gave higher scores than the patients. CONCLUSIONS: Agreements between patients with PD and CG were generally good for most, but not all, of the PDQ-39, SQLC and MCSI domains.

The effect of schooling on reported age of onset of cognitive decline: A collaborative study.

Higher education has been reported to be a protective factor against dementia. We suggest that the strength of a risk factor may be measured by the length of time by which it delays disease onset; therefore, we examined whether people with lower education develop cognitive decline at an earlier age than people with more schooling. The study population was based on patients referred to our Memory Clinics from 1994 to 2004. Analysis of covariance was used to evaluate the effect of schooling on the reported age of memory decline, in patients with mild cognitive impairment (MCI) and in patients diagnosed with Alzheimer's disease (AD). The mean reported age of onset of cognitive decline was unexpectedly lower in patients with higher education than in patients with fewer schooling years, with a relatively small effect size (beta=-0.6), and the effect was more marked in the MCI group. Every year of schooling advanced the reported age of onset by 6months among patients with MCI (t=-6.18, p<.001) and by 3months among patients with AD (t=-2.4, p=0.017). Education may affect the reported age of onset of cognitive decline, but its magnitude is small. It is possible that increased awareness in more educated people leads them to consult earlier; this could explain the paradoxical finding of earlier reported age of onset of cognitive decline in patients with higher education.

Unusual presentations in patients with E200K familial Creutzfeldt-Jakob disease.

BACKGROUND AND PROPOSE: Familial Creutzfeldt-Jakob disease (fCJD) in Jews of Libyan ancestry is caused by an E200K mutation in the PRNP gene. The typical presenting symptoms include cognitive decline, behavioral changes and gait disturbances; however, some patients may have an unusual presentation such as a stroke-like presentation, alien hand syndrome or visual disturbances. The aim of this paper is to describe uncommon presentations in our series of consecutive patients with E200K fCJD. METHODS: The study group included consecutive fCJD patients followed up as part of a longitudinal prospective study ongoing since 2003 or hospitalized since 2005. The clinical diagnosis of probable CJD was based on accepted diagnostic criteria and supported by typical magnetic resonance imaging, electroencephalographic findings, elevated cerebrospinal fluid tau protein levels and by genetic testing for the E200K mutation. Disease symptoms and signs were retrieved from the medical files. RESULTS: The study population included 77 patients (42 men) with a mean age of disease onset of 60.6 ± 7.2 years. The most prevalent presenting symptoms were cognitive decline followed by gait impairment and behavioral changes. However, six patients had an unusual presentation including auditory agnosia, monoparesis, stroke-like presentation, facial nerve palsy, pseudobulbar syndrome and alien hand syndrome. CONCLUSIONS: Our case series illustrates the wide phenotypic variability of the clinical presentation of patients with fCJD and widens the clinical spectrum of the disease. A high level of clinical suspicion may prove useful in obtaining early diagnosis and therefore avoiding costly and inefficient diagnostic and therapeutic strategies.

CSF tau correlates with CJD disease severity and cognitive decline.

BACKGROUND: Creutzfeldt-Jakob disease (CJD) is the most common prion disease in humans. The clinical diagnosis of CJD is supported by a combination of electroencephalogram, MRI, and the presence in the CSF of biomarkers. CSF tau is a marker for neuronal damage and tangle pathology, and is correlated with cognitive status in Alzheimer's disease (AD). OBJECTIVES: The aim of this study was to test whether tau levels in the CSF also correlate with the degree of the neurological deficit and cognitive decline in patients with CJD as reflected by various clinical scales that assess disease severity and cognitive performance. METHODS: Consecutive patients with familial CJD (fCJD) were examined by a neurologist who performed several tests including minimental status examination (MMSE), frontal assessment battery (FAB), NIH stroke scale (NIHSS), CJD neurological scale (CJD-NS), and the expanded disability status scale (EDSS). CSF tau was tested as part of the workout, and the correlation was tested using Pearson correlation. RESULTS: Fifty-two patients with fCJD were recruited to the study (35 males, mean age 59.4 ± 5.7, range 48-75 years). A significant negative correlation was found between CSF tau levels and the cognitive performance of the patients as reflected by their MMSE and FAB scores. In addition, a significant positive correlation was found between tau levels and the clinical disease severity scales of CJD-NS, NIHSS, and EDSS. CONCLUSION: The correlation between tau levels and the disease severity and degree of cognitive decline in patients with fCJD suggests that tau can be a biomarker reflecting the extent of neuronal damage.

What are the correlates of cognition and participation to return to work after first ever mild stroke?

BACKGROUND: The percentage of working age people with mild stroke has risen. Evidence indicates that even mild stroke impact cognition, executive functioning, and daily functioning, consequently affecting participation, quality of life (QoL) and return to work (RTW). OBJECTIVES: (1) Compare cognition, participation and QoL between people 3 months post-mild stroke who RTW and those who did not; and (2) To determine the correlates of these variables to RTW of participants 3 months post-stroke. METHODS: We visited at home 163 stroke survivors (117 men, 46 women) 3 months post-mild stroke ranging from 50 to 89 years. Participants who returned to work (n = 114) and those who did not (n = 49). Data collection at home included measures for cognitive status (MoCA), executive functions (EFPT, DEX), depression (GDS), participation (RNL), and QoL (SIS recovery). RESULTS: Significant differences were found between RTW participants and those who did not RTW in measures of cognition, depression, participation and QoL (t = 2.36 to - 5.62, P < 0.022-0.001). No difference was found on age or gender. Stepwise regression showed that significant correlates of RTW were participation (RNL), executive functions (EFPT), and QoL (SIS recovery). CONCLUSIONS: To enable RTW after mild stroke, participation, executive functions and QoL must be considered in planning interventions.

Cognitive assessment in proximity to acute ischemic stroke/transient ischemic attack: comparison of the montreal cognitive assessment test and mindstreams computerized cognitive assessment battery.

BACKGROUND/AIMS: Even mild stroke survivors may sometimes experience residual cognitive damage. No consensus has emerged about which cognitive test is most appropriate for the diagnosis of poststroke cognitive impairment. We aim to compare a computerized battery of neuropsychological tests for memory, attention and executive functions (MindStreams®) with the Montreal Cognitive Assessment (MoCA) to detect mild-to-moderate cognitive impairments in poststroke patients. METHODS: Subjects enrolled to the TABASCO (Tel Aviv Brain Acute Stroke Cohort) study, a prospective study which includes consecutive first-ever mild-to-moderate stroke patients, were included. All participants underwent neurological and cognitive evaluations. RESULTS: A total of 454 patients with transient ischemic attack (TIA) or stroke are reported. Their mean MoCA and MindStreams scores were lower than normal; however, the TIA group presented significantly better scores using either method. The correlation between the MoCA and the computerized global score was 0.6 (p < 0.001). A significant correlation was found between the subcategory scores (executive function, memory and attention). However, the MoCA identified many more subjects with low scores (<26) compared to the MindStreams (70.6 vs. 15.7%). CONCLUSION: Our results demonstrate that either of the modalities alone is sensitive enough for identifying subtle cognitive impairment and none picks up substantially more cognitive losses than the other in patients with cerebrovascular disease.

Subjective memory complaints in elders: depression, anxiety, or cognitive decline?

OBJECTIVES: To study the association of subjective memory complaints (SMC) with affective state and cognitive performance in elders. MATERIALS AND METHODS: We studied community dwelling elderly persons with normal physical examination. Participants completed questionnaires regarding memory difficulties and lifestyle habits, the Geriatric Depression Scale (GDS) and the Spielberger State-Trait Anxiety Inventory (STAI). Depending on their answers to the question about their memory condition, participants were divided into complainers and non-complainers and to five groups according to their MMSE scores. These data have been compared to objective cognitive performance according to Mindstreams - a computerized neuropsychological battery. A logistic regression was performed to evaluate odds ratios (OR) and 95% confidence intervals (CI) for those factors, which were associated with SMС (dependent variable). RESULTS: Of 636 consecutive subjects (61% females), 507 participants (79.7%) had SMС. Presence of SMC was inversely correlated with MMSE scores, (r = -0.108; P for trend = 0.007). GDS and STAI scores were higher among subjects with SMC (OR = 1.23: CI 95%: 1.1-1.36 and OR = 1.03: CI 95%: 1.01-1.07, respectively). SMC did not correlate with objective cognitive performance measured by Mindstreams. CONCLUSIONS: Subjective memory complaints are associated with sub-syndromal depression and anxiety in healthy cognitively normal elders.

Cerebral white matter disruption in Creutzfeldt-Jakob disease.

BACKGROUND AND PURPOSE: Human prion diseases are known to cause gray matter degeneration in specific cerebral structures, but evidence for white matter involvement is scarce. We used DTI to test the hypothesis that white matter integrity is disrupted in human CJD during the early stages of the disease. MATERIALS AND METHODS: Twenty-one patients with the E200K variant of CJD and 19 controls participated in DTI studies conducted on a 1.5T MR imaging scanner. The data were quantitatively analyzed and mapped with a voxelwise TBSS method. RESULTS: We found significant reductions of FA in patients with CJD in distinct and functionally relevant white matter pathways, including the corticospinal tract, internal capsule, external capsule, fornix, and posterior thalamic radiation. Moreover, these FA deficits increased with disease duration, and were mainly determined by increase of radial diffusivity, suggesting elevated permeability of axonal membranes. CONCLUSIONS: The findings suggest that some of the symptoms of CJD may be caused by a functional dysconnection syndrome, and that the leukoencephalopathy is progressive and detectable fairly early in the course of the disease.

Microembolism, silent brain infarcts and dementia.

Cognitive decline becomes more prevalent than ever in parallel with the increasing life expectancy of the population. Alzheimer' disease (AD) and cerebral vascular lesions are common in the elderly and represent, with increased age, the most frequent contributors to cognitive decline. It is now believed that these pathologies frequently coexist in the same brain. The border discriminating vascular dementia from AD is blurred and challenges our understanding of these clinical entities. Further research, at both basic and clinical levels, is mandatory in order to better understand the interactions of vascular ischemic injury and primary degenerative physiopathologies of the brain, in order to prevent and better manage patients with cognitive decline. We review recent published clinical evidence of silent brain ischemia as a contributor to cognitive decline and dementia. Microemboli, from both cardiac and vascular origins, have been shown to be associated with structural changes in the brain. The role of transcranial Doppler as an objective tool for detecting and quantifying microemboli is discussed in light of recent clinical evidence.

Vasomotor reactivity as a predictor for syncope in patients with orthostatism.

OBJECTIVES: Syncope in patients with orthostatic hypotension (OH) may be the result of impaired cerebral autoregulation. Cerebral autoregulation status can be determined by assessing cerebral vasomotor reactivity (VMR). We assessed and compared VMR in patients with OH with and without syncope. MATERIAL AND METHODS: Twenty-nine patients with OH underwent transcranial Doppler (TCD) and the Diamox test (1 g acetazolamide IV) for assessing VMR during elaboration of their OH syndrome. The percent difference between cerebral blood flow velocities (BFV) in the middle cerebral (MCA) and vertebral (VA) arteries before and after acetazolamide was defined as VMR%. We considered increases of BFV of ≥ 40% as being indicative of good VMR and classified our study patients as having good or impaired VMRs accordingly. RESULTS: Mean VMR% values of the MCA and VA in patients with OH with syncope (n = 12) were significantly lower as compared with patients with OH without syncope (n = 17): 25.2 ± 20.5% and 42.5 ± 18.6%; 20.9 ± 15.5% and 40.8 ± 28.5%, respectively (P < 0.05). CONCLUSIONS: Among patients with OH, we found an association between the presence of syncope and impaired VMR. Assessment of VMR among patients with OH may predict those who are at higher risk to faint and fall and to support more aggressive intervention.

Modeling the dementia epidemic.

The incidence of dementia increases steeply with age in older people, although from the tenth decade the slope may be smoother, perhaps reflecting different pathological processes in the oldest old. The prevalence depends upon interaction of age with other factors (e.g., comorbidities, genetic or environmental factors) that in turn are subject to change. If onset of dementia could be postponed by modulating its risk factors, this could significantly affect its incidence. Analysis of risk and protection factors should take into account the critical period during which these factors play a role. For example, the impact of education and diabetes mellitus occurs in early- and midlife, respectively, while maintaining optimal physical and mental activity and controlling vascular factors later in life may slow the rate of cognitive decline. Modifying factors need to be evaluated for different clinical groups, taking into account genetic background, age, and duration at exposure. The aim of the present article is to try to take stock of epidemiological data concerning factors affecting the prevalence of dementia and predict future developments, as well as to look for possible interventions that could affect outcome.

The Creutzfeldt-Jakob disease (CJD) neurological status scale: a new tool for evaluation of disease severity and progression.

OBJECTIVES: To develop a scale sensitive for the neurological manifestations of Creutzfeldt-Jakob disease (CJD). METHODS: A 26-item CJD neurological status scale (CJD-NS) was created based on characteristic disease manifestations. Each sign was assigned to one of eight neurological systems to calculate a total scale score (TSS) and a system involvement score (SIS). The scale was administered to 37 CJD patients, 101 healthy first-degree relatives of the patients and 14 elderly patients with Parkinson's disease (PD). RESULTS: The mean TSS (±SD) was significantly higher in patients with CJD (13.19 ± 5.63) compared with normal controls (0.41 ± 0.78) and PD patients (9.71 ± 3.05). The mean SIS was also significantly different between the CJD (5.19 ± 1.22) and PD (2.78 ± 1.18 P ≤ 0.01) groups reflecting the disseminated nature of neurological involvement in CJD. Using a cutoff of TSS > 4 yielded a sensitivity of 97% for CJD, and specificity of 100% against healthy controls. All individual items showed excellent specificity against healthy subjects, but sensitivity was highly variable. Repeat assessments of CJD patients over 3-9 months revealed a time-dependent increase in both the TSS and the SIS reflecting the scale's ability to track disease progression. CONCLUSIONS: The CJD-NS scale is sensitive to neurological signs and their progression in CJD patients.

Hemodynamic responses to head-up tilt after spinal cord injury support a role for the mid-thoracic spinal cord in cardiovascular regulation.

BACKGROUND: Data showing a role for the mid-thoracic spinal cord (SC) in the control of hemodynamic changes is scarce despite existing evidence for its involvement in autonomic regulation. STUDY DESIGN: On the basis of the open label prospective series comparing three groups. OBJECTIVE: To determine whether the mid-thoracic SC has a role in hemodynamic regulation during head-up tilt (HUT). SETTING: Spinal Research Laboratory, Loewenstein Rehabilitation Hospital. METHODS: A total of 13 healthy control subjects, 10 patients with T(4)-T(6) paraplegia and 11 with C(4)-C(7) tetraplegia were examined during supine rest and during HUT. Heart rate (HR), blood pressure (BP), HR spectral components (lower frequency fluctuation (LF), higher frequency fluctuations (HF) and LF/HF) and cerebral blood flow velocity (CBFV) were continuously measured or calculated. RESULTS: BP response to HUT differed among these groups (P<0.02). During HUT, BP decreased markedly in the tetraplegia group (from a mean value of 81.65 to 67.69 mm Hg), and increased in the control groups (from 92.89 to 95.44 mm Hg) and in the T(4)-T(6) paraplegia group (from 96.24 to 97.86 mm Hg). Significant correlation was found in the control and tetraplegia groups between increases in HR LF/HF and HR at HUT (r>0.7; P<0.01). No such correlation was found in the paraplegia group. HUT effect on HR and CBFV was significant in all groups (P<0.001), but group differences were statistically non-significant. CONCLUSION: Findings were generally compatible with those of comparable previously published studies, but they also support a role for the mid-thoracic SC in hemodynamic regulation, which should be considered in clinical setting and in research.

The role of apolipoprotein E polymorphisms in levodopa-induced dyskinesia.

OBJECTIVES: To determine the relationship between apolipoprotein E (APOE) polymorphisms to the time to appearance of levodopa-induced dyskinesia (LID) in patients with Parkinson's disease. METHODS: The APOE genotype of 155 consecutive patients treated with levodopa was determined and its effect on the time of onset of LID was examined using Cox regression model, controlling for gender, age of disease onset, time to initiation of levodopa treatment and history of smoking. RESULTS: Two patients were homozygous for the APOE ε2 allele, 7 had ε2/ε3, 1 had ε2/ε4, 130 had ε3/ε3, 12 had ε3/ε4 and 3 had ε4/ε4; LID appeared in 57.4% of the patients, appearing 4.1 ± 3.5 years after the initiation of levodopa treatment. The survival curve for LID was not affected by the APOE genotype (P = 0.34). CONCLUSION: APOE polymorphisms were found not to be associated with either the occurrence or the time to development of LID.

Insulin resistance in tetraplegia but not in mid-thoracic paraplegia: is the mid-thoracic spinal cord involved in glucose regulation?

STUDY DESIGN: Controlled experimental human study. OBJECTIVES: To assess insulin resistance (IR) in tetraplegia and paraplegia, and the role of the spinal cord (SC) in glucose regulation. SETTING: Laboratory of Spinal Research, Loewenstein Rehabilitation Hospital. METHODS: Glucose and insulin levels and the heart rate variation spectral components LF (low frequency), HF (high frequency) and LF/HF were studied at supine rest, head-up tilt and after a standard meal in three groups: 13 healthy subjects, 7 patients with T(4)-T(6) paraplegia and 11 patients with C(4)-C(7) tetraplegia. RESULTS: Glucose and insulin increased significantly after the meal in all groups (P<0.001). Glucose increased significantly more in the tetraplegia than in the other groups (P<0.01). Increases in insulin level tended to accompany increases in LF/HF after the meal in the tetraplegia and control groups but not in the paraplegia group. CONCLUSION: Post-prandial IR appears in C(4)-C(7) but not in T(4)-T(6) SC injury. The results of the study, combined with previously published findings, are consistent with the hypotheses that IR is related to activation of the sympathetic nervous system, and that below T(4) the mid-thoracic SC is involved in the regulation of glucose and insulin levels.

Female sexuality in multiple sclerosis: the multidimensional nature of the problem and the intervention.

Female sexual functioning is a complex process involving physiological, psychosocial and interpersonal factors. Sexual dysfunction (SD) is frequent (40-74%) among women with multiple sclerosis (MS), reflecting neurological dysfunction, psychological factors, depression, side effects of medications and physical manifestations of the disease, such as fatigue and muscle weakness. A conceptual model for sexual problems in MS characterizes three levels. Primary SD includes impaired libido, lubrication, and orgasm. Secondary SD is composed of limiting sexual expressions due to physical manifestations. Tertiary SD results from psychological, emotional, social, and cultural aspects. Sexual problems cause distress and may affect the family bond. Practical suggestions on initiation of discussion of sexual issues for MS patients are included in this review. Assessment and treatment of sexual problems should combine medical and psychosexual approaches and begin early after MS diagnosis. Intervention can be done by recognizing sexual needs, educating and providing information, by letting patients express their difficulties and referring them to specialists and other information resources.