José Enrique Martínez-Rodríguez

Rapid eye movement sleep behavior disorder and potassium channel antibody–associated limbic encephalitis

Of six patients registered in our center with nonparaneoplastic limbic encephalitis associated with antibodies to voltage‐gated potassium channels, the five men had rapid eye movement sleep behavior disorder (RBD) coincident with voltage‐gated potassium channel antibody–associated limbic encephalitis onset. In three patients, immunosuppression resulted in resolution of RBD in parallel with remission of the limbic syndrome. RBD persisted in two patients with partial resolution of the limbic syndrome. Our findings suggest that RBD is frequent in the setting of voltage‐gated potassium channel antibody–associated limbic encephalitis and can be related to autoimmune‐mediated mechanisms. In addition, these observations suggest that impairment of the limbic system may play a role in the pathogenesis of RBD. Ann neurol 2006

Nonconvulsive status epilepticus associated with cephalosporins in patients with renal failure

PURPOSE Nonconvulsive status epilepticus is an unusual complication of cephalosporin therapy, with only a few isolated cases reported. SUBJECTS AND METHODS We reviewed the clinical and electroencephalographic (EEG) characteristics of 10 patients with renal failure in whom developed alteration of consciousness without convulsions associated with continuous epileptiform EEG activity while being treated with cephalosporins. RESULTS Nonconvulsive status epilepticus developed in 5 men and 5 women, with a mean (+/- SD) age of 69 +/- 14 years, while receiving intravenous cephalosporins (ceftriaxone, 2 patients; ceftazidime, 2; and cefepime, 6). All patients had renal failure; 1 also had hepatic failure. Patients presented with progressive disorientation or agitation, sometimes associated with mild facial or limb myoclonus, that had begun 1 to 10 days (mean, 5 +/- 2 days) after starting cephalosporin treatment. The EEG showed continuous or intermittent bursts of generalized, high-voltage, 1 to 2 Hz sharp wave activity or sharp and slow wave activity that resembled, but could be differentiated from, the triphasic waves seen in metabolic encephalopathies. Intravenous clonazepam suppressed the epileptiform activity completely in 5 patients and partially in the other 5. Cephalosporins were withdrawn, and antiepileptic therapy was started for all patients. All patients improved, 2 in less than 24 hours and the remainder within 2 to 7 days. CONCLUSIONS Cephalosporins can cause nonconvulsive status epilepticus in patients with renal failure. The clinical picture is difficult to differentiate from a that of metabolic encephalopathy unless an EEG is obtained. Physicians should be aware of this potentially dangerous complication.

Steno-occlusive arterial disease and early neurological deterioration in acute ischemic stroke.

Aim: To evaluate the influence that steno-occlusive arterial disease may have on the development of early neurological deterioration (END) in a large series of patients with acute ischemic stroke. Methods: We studied a prospective cohort of 1,093 patients admitted to a single tertiary hospital with presence of neurological symptoms in the first 24 h after stroke onset. END was defined as any increase in the National Institutes of Health Stroke Scale score ≧4 points in the first 72 h. The arterial study assessed the presence of arterial occlusion or significative stenosis in the symptomatic territory. Additionally, age, initial stroke severity, blood pressure, glucose levels, vascular risk factors, lacunar stroke and prior use of antithrombotic treatment were also analyzed in a multivariable analysis. Results: END was detected in 179 patients (16.3%). Steno-occlusive disease (adjusted OR 3.60), initial blood pressure and abdominal obesity were independently associated with END. Both arterial stenosis (adjusted OR 2.33) or occlusions (adjusted OR 3.65) were associated with END. The higher adjusted OR (5.49) was obtained for steno-occlusive arterial disease in the vertebrobasilar system. Conclusions: An early arterial study may provide key data for the selection of patients with higher risk of END after acute ischemic stroke.

Changes in dreaming induced by CPAP in severe obstructive sleep apnea syndrome patients

To study dream content in patients with severe obstructive sleep apnea syndrome (OSAS) and its modification with Continuous Positive Airway Pressure (CPAP) therapy. We assessed twenty consecutive patients with severe OSAS and 17 healthy controls. Polysomnograms were recorded at baseline in patients and controls and during the CPAP titration night, 3 months after effective treatment and 2 years later in patients. Subjects were awakened 5–10 min after the beginning of the first and last rapid eye movement (REM) sleep periods and we measured percentage of dream recall, emotional content of the dream, word count, thematic units, sleep architecture and REM density. Dream recall in REM sleep was similar in patients at baseline and controls (51.5% versus 44.4% respectively; P = .421), decreased to 20% and 24.3% the first and third month CPAP nights, and increased to 39% 2 years later (P = 0.004). Violent/highly anxious dreams were only seen in patients at baseline. Word count was higher in patients than in controls. REM density was highest the first CPAP night. Severe OSAS patients recall dreams in REM sleep as often as controls, but their dreams have an increased emotional tone and are longer. Despite an increase in REM density, dream recall decreased the first months of CPAP and recovered 2 years later. Violent/highly anxious dreams disappeared with treatment. A dream recall decrease with CPAP is associated with normalization of sleep in OSAS patients.

Manometric correlations of anorectal dysfunction and biofeedback outcome in patients with multiple sclerosis

Objective To evaluate clinical and manometric characteristics of multiple sclerosis (MS) patients with anorectal dysfunction (ARD) and their influence on biofeedback outcome. Patients and methods Patients were clinically and manometrically studied and compared with controls. Patients were subsequently offered to initiate biofeedback manoeuvres to improve ARD. Results Fifty-two patients with ARD, 39 women, mean age 44.96 ± 9.26 years, mean Expanded Disability Status Scale 4.13 ± 1.72, were evaluated. Thirty-one patients had relapsing-remitting (RR), 16 secondary progressive and five primary progressive MS. ARD complaints were constipation (67.3%), double ARD (23.1%) and isolated incontinence (9.6%). The manometric study showed significant differences in patients compared with controls in maximal contraction pressures (98.1 ± 44.2 mm Hg versus 152.05 ± 66.9 mm Hg, P < 0.001) and anal inhibitory reflex threshold (92.9 ± 63.4 mL versus 40.45 ± 11.3 mL, P < 0.001). Maximal pressure was lower in progressive forms compared with RR forms (83.1 ± 36.2 mm Hg versus 108.2 ± 46.7 mm Hg, P < 0.05) in relation to higher disability. Patients with paradoxical contraction (PC) (35 patients, 67.3%) showed more manometric disturbances. From a total of 18 patients performing biofeedback, those reporting some improvement (six complete, two partial) had milder manometric abnormalities. Conclusions The most frequent manometric abnormalities in our MS patients with ARD were alterations of maximal pressures, anal inhibitory reflex and PC. Biofeedback could be more useful in patients with lower disability and manometric alterations. Multiple Sclerosis 2008; 14: 237—242. http://msj.sagepub.com

Cerebrospinal fluid hypocretin-1 levels in multiple system atrophy

Hypocretin (orexin) cerebrospinal fluid (CSF) levels have been previously found normal or decreased in Dementia with Lewy bodies and Parkinson disease, two synucleinopathies commonly associated with excessive daytime sleepiness (EDS). We evaluated CSF hypocretin‐1 levels in 15 patients with moderately severe multiple system atrophy (MSA), another synucleinopathy where sleep disorders occur frequently and EDS has been reported, performing additional electrophysiological studies in 5 of them to assess the presence of EDS and sleep onset REM (SOREM) periods. Despite relatively low sleep efficiencies in nocturnal sleep, mean sleep latencies in the Multiple Sleep Latency Test were normal with no SOREM periods. All patients had CSF hypocretin‐1 levels in the normal range (>200 pg/mL) suggesting that the hypocretin system is not altered in MSA, at least in patients with a moderately severe disease.

Previous Infection and Stroke: A Prospective Study

Background: Previous studies have demonstrated that infections might precipitate ischemic strokes (IS). We sought to describe, in a large prospective series, the frequency of previous infection (PI) in IS and intracerebral hemorrhage (ICH), and to assess whether any relationship with stroke subtype or outcome could be identified. Methods: Between January 2005 and December 2010, we studied 1,981 patients with acute stroke. The presence of PI within the month before the stroke was prospectively assessed. PI was correlated with demographic data, vascular risk factors, stroke subtype, and 3-month outcome. Results: A total of 193 (9.7%) patients had suffered a PI, the most common being respiratory tract infections (36.8%), flu or flu-like illness (30.1%), and gastrointestinal infections (12.4%). PI was more frequent in IS cases (10.2%) than in ICH (6.8%) (p = 0.081). Among IS cases, no differences were seen between PI and TOAST subtypes (p = 0.644). For IS, patients with PI were older (p = 0.025), had worse previous functional status (p = 0.002), suffered a more severe stroke (p = 0.002), achieved poor outcome (p = 0.001), and had higher 3-month mortality (p = 0.019). Multivariate analysis showed that IS patients with PI had previous poor functional status (OR = 1.58; p = 0.026) and suffered more severe strokes (OR = 1.02, p = 0.048). After adjustment for confounders, PI has no independent influence on 3-month outcome (OR = 1.15; p = 0.564). Conclusions: PI are observed in 9.7% of stroke cases without differences according to the TOAST subtype. PI are associated with previous poor functional status and with stroke severity, but have no independent influence on the 3-month outcome.

Expansion of the NKG2C+ Natural Killer–Cell Subset Is Associated With High-Risk Carotid Atherosclerotic Plaques in Seropositive Patients for Human Cytomegalovirus

Objective—Human cytomegalovirus (HCMV), a pathogen involved in the development and progression of atherosclerosis, promotes in some individuals a marked reconfiguration of the natural killer (NK)–cell compartment whose hallmark is a persistent expansion of a peripheral blood NK-cell subset expressing the CD94/NKG2C NK receptor. We aimed to evaluate whether the HCMV-associated NK-cell compartment reconfiguration is related to carotid atherosclerotic plaque (CAP) instability. Approach and Results—NK receptor expression (ie, LILRB1, NKG2A, NKG2C, and killer immunoglobulin-like receptors [KIR]) by peripheral NK and T cells was evaluated in 40 patients with HCMV+ with CAP, including nonatherosclerotic strokes (n=15) and healthy subjects (n=11) as controls. High-risk CAP (n=16), defined as carotid stenosis >50% with ipsilateral neurological symptomatology in the previous 180 days, compared with non–high-risk CAP had higher %NKG2C+ NK cells (29.5±22.4% versus 16.3±13.2%; P=0.026; odds ratio, 1.053; 95% confidence interval, 1.002–1.106; P=0.042), with a corresponding reduction in the NKG2A+ NK subset (31.7±17.8% versus 41.8±15.8%; P=0.072). The proportions of NKG2C+ NK cells in high-risk CAP were inversely correlated with the CD4+/CD8+ ratio (RSpearman=−0.629; P=0.009) and directly with high-sensitivity C-reactive protein levels (RPearson=0.591; P=0.012), consistent with higher subclinical systemic inflammation. The intraplaque inflammatory infiltrate, evaluated in 27 CAP obtained after endarterectomy, showed a higher presence of subintimal CD3+ lymphocytes in those patients with HCMV-induced changes in the peripheral NK- and T-cell compartments. Conclusions—The expansion of NKG2C+ NK cells in patients with CAP seems to be associated with an increased risk of plaque destabilization in some patients with chronic HCMV infection.

Four year follow-up study after unilateral pallidotomy in advanced Parkinson's disease.

Abstract.Background: Pallidotomy is widely accepted as a treatment for patients with Parkinsons disease (PD) who have disabling symptoms that are inadequately controlled with pharmacotherapy. There are, however, only a few studies, with a small number of patients, showing evidence after prolonged periods of time about the clinical outcome after pallidotomy. Methods: We have conducted a four-year follow-up study of 23 patients with PD who had undergone unilateral pallidotomy. Six patients were lost to follow-up. The remaining 17 were evaluated before surgery and at three months, one year, and four years after surgery, following standard protocols. Results: At four years, patients still showed significant amelioration in contralateral and axial dyskinesias and off-period contralateral parkinsonian signs. Total motor UPDRS and Activities of Daily Living scores also remained improved four years after surgery. Ipsilateral and axial parkinsonian symptoms and Hoehn & Yahr and Schwab & England scales were not significantly changed from baseline values. The initial beneficial effects on motor fluctuations were not maintained at last visit. All patients considered themselves to be improved with respect to their clinical condition before surgery in a clinical global impression estimation done at the four-year follow-up. Conclusion: Unilateral pallidotomy can provide sustained improvement of contralateral parkinsonism and dyskinesias during at least four years. Early benefits observed in axial symptoms and motor fluctuations wane with time. On period akinesia worsened significantly in the limbs contralateral to pallidotomy after four years.

Periodic hyperthermia and abnormal circadian temperature rhythm in a patient with multiple sclerosis

Disturbances of the central thermoregulation in patients with multiple sclerosis (MS) are not often reported. We describe a 45-year old patient with a 13-year history of MS, who developed a clinical picture of recurrent hyperthermia. MRI showed a bilateral involvement of the hypothalamus in the setting of diffuse white matter disease. Serial body temperature measurement for five consecutive months disclosed an inversion of the circadian temperature rhythm. The clinical presentation and MRI findings suggested abnormalities of the central thermal control in relation to MS widespread involvement of the central nervous system (CNS).