Search

ObjectiveTo report 3 patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who developed generalized myoclonus.MethodsPatient data were obtained from medical records from the University Hospital “12 de Octubre,” Madrid, Spain.ResultsThree patients (2 men and 1 woman, aged 63–88 years) presented with mild hypersomnia and generalized myoclonus following the onset of the so-called inflammatory phase of coronavirus disease 2019 (COVID-19). All of them had presented previously with anosmia. Myoclonus was generalized with both positive and negative jerks, predominantly involving the facial, trapezius, sternocleidomastoid, and upper extremities muscles. These myoclonic jerks occurred spontaneously and were extremely sensitive to multisensory stimuli (auditive and tactile) or voluntary movements, with an exaggerated startle response. Other causes of myoclonus were ruled out, and none of the patients had undergone respiratory arrest or significant prolonged hypoxia. All of them improved, at least partially, with immunotherapy.ConclusionsOur 3 cases highlight the occurrence of myoclonus during the COVID-19 pandemic as a post- or para-infectious immune-mediated disorder. However, we cannot rule out that SARS-CoV-2 may spread transneuronally to first- and second-order structures connected with the olfactory bulb. Further investigation is required to clarify the full clinical spectrum of neurologic symptoms and optimal treatment.

ObjectiveTo report 2 patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who presented acutely with Miller Fisher syndrome and polyneuritis cranialis, respectively.MethodsPatient data were obtained from medical records from the University Hospital “Príncipe de Asturias,” Alcalá de Henares, and the University Hospital “12 de Octubre,” Madrid, Spain.ResultsA 50-year-old man presented with anosmia, ageusia, right internuclear ophthalmoparesis, right fascicular oculomotor palsy, ataxia, areflexia, albuminocytologic dissociation, and positive testing for anti-GD1b–immunoglobulin G antibody. Five days previously, he had developed a cough, malaise, headache, low back pain, and fever. A 39-year-old man presented with ageusia, bilateral abducens palsy, areflexia, and albuminocytologic dissociation. Three days previously, he had developed diarrhea, a low-grade fever, and poor general condition. Oropharyngeal swab test for SARS-CoV-2 by qualitative real-time reverse transcriptase PCR assay was positive in both patients and negative in the CSF. The first patient was treated with IV immunoglobulin and the second with acetaminophen. Two weeks later, both patients made a complete neurologic recovery, except for residual anosmia and ageusia in the first case.ConclusionsOur 2 cases highlight the rare occurrence of Miller Fisher syndrome and polyneuritis cranialis during the coronavirus disease 2019 (COVID-19) pandemic. These neurologic manifestations may occur because of an aberrant immune response to COVID-19. The full clinical spectrum of neurologic symptoms in patients with COVID-19 remains to be characterized.

We thank Dr. Vavougios and Vaira et al. for their letters on our study,1 which reported 2 patients infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) who acutely presented with Miller Fisher syndrome and polyneuritis cranialis, respectively. We agree with Dr. Vavougios that indolent self-limiting neuroinvasion could manifest as self-limiting anosmia, whereas the ganglioside-virus interaction would offer a prominent target for an antiganglioside antibody response as in our patient with Miller Fisher syndrome. In addition, we also agree with Dr. Vaira et al. regarding anosmia in coronavirus disease 2019 (COVID-19). Indeed, SARS-CoV-2 could negatively influence the activity of olfactory neurons through inflammatory mechanisms. Further study is needed regarding whether ageusia could instead be caused by the direct action of the SARS-CoV-2 on the ACE-2 receptors of the taste buds.

Parkinson disease (PD) is a chronic progressive neurodegenerative disorder with a relatively high incidence.1 PD seems to result from a complicated interplay of genetic and environmental factors affecting numerous fundamental cellular processes.2 However, the ultimate cause of loss of dopaminergic neurons in the substantia nigra pars compacta remains to be determined.2 An outright definitive cure for the disease remains elusive, leaving both patients and their caregivers with the challenge of living with a chronic medical condition that affects their health-related quality of life.2 It is therefore imperative to focus research efforts on the search for the etiology of this condition.

Objective: To determine in a population-based study whether long sleep duration was associated with increased risk of dementia mortality. Methods: In this prospective, population-based study of 3,857 people without dementia aged 65 years and older (NEDICES [Neurological Disorders in Central Spain]), participants reported their daily sleep duration. The average daily total sleep duration was grouped into 3 categories: ≤5 hours (short sleepers), 6–8 hours (reference category), and ≥9 hours (long sleepers). Community-dwelling elders were followed for a median of 12.5 years, after which the death certificates of those who died were examined. Results: A total of 1,822 (47.2%) of 3,857 participants died, including 201 (11.0%) deaths among short sleepers, 832 (45.7%) among long sleepers, and 789 (43.3%) among those participants in the reference category. Of 1,822 deceased participants, 92 (5.1%) had a dementia condition reported on the death certificate (49 [53.3%] were long sleepers, 36 [39.1%] reported sleeping between 6 and 8 hours, and 7 [7.6%] were short sleepers). In an unadjusted Cox model, risk of dementia-specific mortality was increased in long sleepers (hazard ratio for dementia mortality in long sleepers = 1.58, p = 0.04) when compared with the reference group. In a Cox model that adjusted for numerous demographic factors and comorbidities, the hazard ratio for dementia mortality in long sleepers was 1.63 ( p = 0.03). Conclusions: Self-reported long sleep duration was associated with 58% increased risk of dementia-specific mortality in this cohort of elders without dementia. Future studies are required to confirm these findings.

Huntington disease (HD) is a relentlessly progressive neurogenetic disorder. The classical clinical features include choreiform movements, mood swings, and memory loss. The huntingtin gene contains a triplet repeat CAG expansion, and generally the larger the expansion, the more severe and earlier the onset of symptoms. Diagnosis and management of HD has come a long way since the last century, when neurologists had to make a diagnosis on purely clinical grounds and often sent the patient away with little hope. We know how common HD is (a prevalence of ∼10–15/100,000), and that presymptomatic genetic testing of family members is infrequently pursued (around 14%).1,2 We also know that the age at onset of symptoms is determined by the normal HD gene, and other modifier genes and environmental factors, and not just the CAG repeat size.3–5

Background: A two-phase investigation method (screening followed by detailed examination) is the most accurate epidemiologic approach to estimate the epidemiology of Parkinson disease (PD) and secondary parkinsonism. The scarcity of statistics on the incidence of PD and other types of parkinsonism using this methodology led the authors to estimate them in three elderly populations. Methods: A Spanish elderly parkinsonism-free cohort was followed for an average of 3 years. At the end of the follow-up, the cohort survivors were contacted by way of screening and clinical examination. Results: The cohort consisted of 5,160 subjects (ages 65 to 85 and over): Eight hundred twenty-eight died before the examination, 3,685 completed the screening procedure, and 647 could not be screened because they refused (108) or were unreachable (539). Sixty-eight incident cases of parkinsonism were found: 30 PD (44.1%), 22 drug-induced parkinsonism (32.3%), 8 parkinsonism with associated features (11.7%), and 3 vascular parkinsonism (4.4%). The remaining five cases (7.3%) were classified as unspecified parkinsonism. Average annual incidence rate (per 100,000 person-years) in the population aged 65 to 85 and over years, adjusted to the standard European population, was 409.9 (95% CI 299.0 to 520.8) for parkinsonism and 186.8 (95% CI 110.4 to 263.2) for PD. Incidence rates of parkinsonism increased with advancing age. For PD, incidence rates increased with age in men but decreased beyond the age of 79 in women. Age-adjusted relative risk in men compared with women was 1.56 (95% CI 0.97 to 2.51) for parkinsonism and 2.55 (95% CI 1.21 to 5.37) for PD. Sixteen (53.3%) patients with PD were detected through the screening and had not been diagnosed previously. Conclusions: Incidence estimates of PD based on two-phase investigation methodology are higher than those based on other approaches. Men had a risk of developing PD that was twice that of women. A large proportion of PD patients may never seek neurologic attention.

Objective: To assess whether faster cognitive decline in elders without dementia is associated with decreased risk of cancer mortality. Methods: In this population-based, prospective study of 2,627 people without dementia aged 65 years and older (Neurological Disorders in Central Spain), a 37-item version of the Mini-Mental State Examination (37-MMSE) was administered at 2 visits (baseline and follow-up, approximately 3 years later). We divided change in 37-MMSE into tertiles (lower tertile ≥2 point improvement in score, higher tertile ≥2 point decline in score). Community-dwelling elders were followed for a median of 12.9 years, after which the death certificates of those who died were examined. Results: A total of 1,003 (38.2%) died, including 339 (33.8%) deaths among participants who were in the higher tertile of 37-MMSE change and 664 (66.2%) deaths among those in the remaining tertiles. Cancer was reported significantly less often in those in the higher tertile of MMSE change (20.6%) than in those in the remaining tertiles (28.6%): in an unadjusted Cox model, hazard ratio for cancer mortality in participants within the higher tertile = 0.75 ( p = 0.04) compared with the participants within the remaining tertiles. In a Cox model that adjusted for a variety of demographic factors and comorbidities, hazard ratio for cancer mortality in participants within the higher tertile = 0.70 ( p = 0.01). Conclusion: In this population-based, prospective study of community-dwelling elders without dementia, faster cognitive decline was associated with a decreased risk of cancer mortality. Further studies are required to elucidate this inverse association in elders without dementia.

Objective: To characterize the rate of cognitive decline during the premotor phase of essential tremor (ET) in comparison to prevalent ET cases and controls. Methods: In this population-based, prospective study of people aged 65 years and older (Neurological Disorders in Central Spain), a 37-item version of the Mini-Mental State Examination was administered at 2 visits (baseline and follow-up, approximately 3 years later). We compared the rate of cognitive decline in 3 groups: prevalent ET cases (i.e., participants diagnosed with ET at baseline and at follow-up), “premotor” ET cases (i.e., participants diagnosed with incident ET at follow-up, but not at baseline), and controls (i.e., participants not diagnosed with ET at baseline or follow-up). Results: The 2,375 participants included 135 prevalent ET cases, 56 premotor ET cases, and 2,184 controls. During the follow-up period of 3.4 ± 0.5 years (mean ± SD), the 37-item version of the Mini-Mental State Examination declined by 0.7 ± 3.3 points (0.2 ± 1.0 points/year) in prevalent ET cases, 1.1 ± 3.5 points (0.3 ± 1.0 points/year) in premotor ET cases, and 0.1 ± 3.9 points (0.0 ± 1.2 points/year) in controls ( p = 0.014). The difference between premotor ET cases and controls was significant ( p = 0.046), as was the difference between prevalent ET cases and controls ( p = 0.027). Conclusions: In this prospective cohort, cognitive test scores in premotor and prevalent ET cases declined at a faster rate than in elders without this disease. A decline in global cognitive function may occur in a premotor phase of ET.

Editors' Note: Drs. Benito-Leon and Domingo-Santos express their surprise at the lack of apparent cerebellar involvement in the “Orthostatic tremor: Clinical, electrophysiologic, and treatment findings in 184 patients” study. They also suggest that orthostatic tremor (OT) may be part of other neurologic disorders such as Parkinson disease (PD) or parkinsonism. Hassan et al., authors of the study, highlight the lack of evidence for cerebellar involvement and are hopeful for a better unifying pathophysiology to explain OT. Boyd et al. believe that there is an association between hepatitis C virus treatment and development of PD and ask the authors of “Hepatitis C virus infection as a risk factor for Parkinson disease: A nationwide cohort study” to …

Background: Although data are sparse, people with essential tremor (ET) are usually assumed to have mortality rates similar to those in the general population. Because ET is common, particularly among older adults, an influence of ET on the life span would have important public health implications. The authors compared the risks of mortality in patients with ET and control subjects without ET.Methods: A prospective, population-based design was used to compare the risk of mortality in participants with ET vs controls in three communities in central Spain. Participants were evaluated at baseline (1994 to 1995) and at follow-up 3 years later (1997 to 1998). The relative risk (RR) of mortality (ET vs controls) was estimated using Cox proportional hazards models that excluded participants with Parkinson disease or dementia.Results: Mean baseline age was 73.5 ± 6.4 years. There were 33 (16.4%) deaths among 201 ET cases and 465 (13.9%) among 3,337 controls. In an unadjusted Cox model, risk of mortality was increased in ET (RR = 1.59, 95% CI = 1.11 to 2.27, p = 0.01). In a Cox model that adjusted for baseline age, gender, educational category, current ethanol drinking, use of antidepressant medication, and community, RR = 1.45, 95% CI = 1.01 to 2.08, p = 0.04. In an adjusted Cox model restricted to persons with longer (>3 years) follow-up, RR = 4.69 (95% CI = 2.18 to 10.07, p = 0.001).Conclusions: In this longitudinal, prospective study, the risk of mortality was increased in essential tremor. Additional studies of incident cases are needed to confirm these results.

Editors' Note: Dr. Kawada raises concerns about the statistics in “Long sleep duration in elders without dementia increases risk of dementia mortality (NEDICES).” Authors Benito-Leon et al. address his concerns. Drs. Mahlknecht et al. describe their own study that concluded that hyposmia is associated with an increased risk of developing motoric cognitive risk syndrome, as reported by Verghese et al. in “Motoric cognitive risk syndrome: Multicenter incidence study.” The authors respond that understanding such links between noncognitive function and dementia risk may be able to improve …

Objective: To determine whether essential tremor (ET) is associated with prevalent dementia. Methods: The authors identified all persons with dementia and ET in a population-based study in central Spain (the Neurological Disorders in Central Spain [NEDICES] Study). Dementia was diagnosed using the Diagnostic and Statistical Manual of Mental Disorders (4th ed.) criteria. Results: Thirty-one (11.4%) of 273 ET cases had dementia vs 204 (6.0%) of 3,382 non-ET subjects (controls) (odds ratio [OR] = 2.00, 95% CI = 1.34 to 2.98, p = 0.001). In a model that adjusted for age, stroke, and educational level, OR = 1.35, 95% CI = 0.87 to 2.18, and p = 0.17. In an adjusted model, ET cases with tremor onset after age 65 were 70% more likely to be demented than were controls (OR = 1.70, 95% CI = 1.04 to 2.76, p = 0.03), whereas ET cases with tremor onset at age ≤65 and controls were equally likely to be demented (OR = 0.38, 95% CI = 0.09 to 1.73, p = 0.21). Conclusions: Older-onset essential tremor (ET) was associated with dementia. Prospective studies are required to elucidate the association between ET and dementia.

To determine whether patients with essential tremor (ET) have cognitive deficits when compared with controls and whether the types of cognitive deficits reported previously are also found in this large sampling of patients with ET.A total of 232 patients with ET and 696 matched controls age 65 years or older (median 75 years) living in central Spain (the Neurologic Diseases in Central Spain study) underwent a neuropsychological assessment, including tests of global cognitive performance, frontal executive function, verbal fluency, and memory. Subjects also were asked whether they had forgetfulness.Fifty-six patients with ET were previously undiagnosed; only 14 (6%) were taking medication for tremor. Adjusted for age, gender, education, premorbid intelligence, medications, and depressive symptoms, cases performed less well on most neuropsychological tests and especially tests of global cognitive performance (37-item Mini-Mental State Examination = 27.0 +/- 6.7 in cases vs 28.9 +/- 5.9 in controls, p0.001) and frontal executive function (Trail Making Test number of errors = 8.7 +/- 11.0 in cases vs 3.8 +/- 7.6 in controls, p0.001). Forgetfulness was reported in 117 (50.4%) patients with ET vs 300 (43.1%) controls (p = 0.05).In a population-based sample of largely untreated patients with essential tremor, cases performed more poorly on formal neuropsychological testing than did their counterparts without tremor. A complaint of forgetfulness was also marginally more common in patients with essential tremor.

Orthostatic tremor (OT) is a rare movement disorder that consists of involuntary shaking of the legs and trunk present only on standing. Although the origin and the mechanism of this condition are not well understood, the neurophysiologic abnormalities and PET studies suggest a central origin. We describe the clinical and radiologic features of two patients with symptomatic OT and associated pontine lesions, and conclude that OT may arise from dysfunction of the cerebellum or related pontine structures.

Article abstract-We studied respiratory chain enzyme activities in lymphocyte mitochondria from 33 patients with Alzheimer's disease (AD) and from 30 age- and sex-matched healthy controls. The respiratory chain enzyme activities did not differ significantly between patients and controls. No patient showed any value for respiratory chain enzyme levels below normal range. Values for activities of complexes in the AD group did not correlate with age at onset or duration of the disease. Our finding of normal mitochondrial function in lymphocyte mitochondria suggests that this tissue cannot be used to demonstrate the involvement of oxidative phosphorylation in AD and, thus, to develop a diagnostic test for AD.NEUROLOGY 1997;48: 636-638

Objective: To estimate the incidence of essential tremor (ET) in three populations in central Spain using data from the Neurologic Disorders in Central Spain (NEDICES), a population-based survey of elderly subjects (65 years and older). Methods: Individuals were evaluated at baseline (1994 to 1995) and at follow-up (a median of 3.3 years later in 1997 to 1998). The evaluation included a screening question for ET and a neurologic examination, when possible. Results: Of 5,278 subjects evaluated at baseline, there were 256 prevalent ET cases. Eighty-three incident ET cases were identified among 3,942 individuals assessed at follow-up. The adjusted annual incidence rate (per 100,000 person-years) in the population aged 65 years and older was 616 (95% CI: 447 to 784). Sixty-four (77.1%) of 83 incident cases had not been diagnosed before our assessment. Conclusions: The incidence of ET may be higher than previously recognized because a large proportion of patients with ET may never seek medical attention.

Article abstract-The authors analyzed whether the pituitary gland enlarges in intracranial hypotension syndrome by studying 11 consecutive patients. Initial MRI scans showed pituitary gland enlargement with a convex superior margin. Follow-up MRI studies revealed that the size of the gland invariably diminished in all patients. The authors hypothesize that pituitary gland enlargement in intracranial hypotension syndrome is due to hyperemia of dural and epidural venous sinuses.

Alexia without agraphia (pure alexia) is considered one of the classic disconnection syndromes. Patients are unable to recognize visual letter or word symbols, but retain the ability to write and often have right homonymous hemianopia.1 Pure alexia without a visual defect is a rare variant.1-3 Few reports show pathologic verification of the correlation of the lesions location or clinical-neuroimaging. We describe a patient with pure alexia without hemianopia as the first published example caused by a spontaneous hematoma involving extrastriate visual cortex of the left occipital lobe, demonstrated on MRI and single-photon emission computed tomography(SPECT). Case report. A 40-year-old right-handed man with a history of minimal change glomerulonephritis and long-standing hypertension was otherwise well until the day of admission, when he had an acute occipital headache and inability to read. Aside from a blood pressure of 150/95 mm Hg, the general examination on admission was unremarkable. Neurologic examination revealed him to be oriented clearly and alert with fluent speech. He could name, repeat, and comprehend appropriately. He was able to write …

Objective: Our objective was to analyze the association of tic disorders with poor school performance. Background Tic disorders have been associated with academic difficulties, but this association has not been explored in detail. Design/Methods: In this cross sectional, observational study in Burgos (Spain), we randomly selected a sample of mainstream schoolchildren (age 6-16 years). The sampling frame included different types of schools and educational levels. We identified students with poor school performance (repeating a grade, special needs) and tic disorders (defined using DSM-IV TR criteria). Children with vs. without tics and those with vs. without poor school performance were compared in terms of clinical features (medical history, neurological and psychiatric comorbidities), school and environment characteristics. Logistic regression analyses were conducted using school performance as the dependent variable, and tic disorders as the independent variable, adjusting for confounding variables. Results: We included 1,867 children [mean age 10.9 + 2.9 years, 1,007 (53.9%] males). Tics were present in 162 children (8.6%) and poor school performance in 223 (11.9%). After adjusting for confounding variables, tic disorders were not associated with poor school performance. Instead, poor school performance was associated with the need of academic support at school [adjusted odds ratio (OR)=4.13, p=0.01), increased age (OR=2.01, p Conclusions: In contrast to previous reports, tic disorders were not associated with academic difficulties. Different methodology, sample, and school system characteristics may account for this discrepancy. Modification of environment variables, including early academic support, and limitation of TV viewing may be potentially associated with better school performance. Supported by: SACYL, Biomedicine project GRS 157-A, Health Research Grant PI 070846, and the European General Development Co-funding. Disclosure: Dr. Cubo Delgado has received personal compensation for activities with GlaxoSmithKline, Inc., UCB Pharma, Italfarmaco, and Boehringer Ingelheim Pharmaceuticals, Inc. Dr. Trejo has received personal compensation for activities with Pfizer Inc, Servier Laboratories, Sanofi-Aventis Pharmaceuticals Inc. and Esteve. Dr. Ausin-Villaverde has nothing to disclose. Dr. Saez has nothing to disclose. Dr. Delgado-Benito has nothing to disclose. Dr. Macarron-Vicente has nothing to disclose. Dr. Louis has nothing to disclose. Dr. Cordero-Guevara has nothing to disclose. Dr. Benito-Leon has nothing to disclose.

Numb chin syndrome, which consists of focal sensory loss and paresthesias of the chin, occurs with malignant diseases. We report a patient with numb chin syndrome, caused by Burkitt's lymphoma, occurring as the initial manifestation of HIV infection.

Reply from the Authors: We appreciate the comments offered by Mark to our article concerning the possibility that pure alexia might not be a disconnection syndrome. In response to his question concerning the fact that our patient could have sustained a "physiologic" …

We studied respiratory-chain enzyme activities in lymphocyte mitochondria from 36 untreated Parkinson's disease (PD) patients and in 30 age- and sex-matched healthy controls. The respiratory-chain enzyme activities did not differ significantly between patients and controls. Moreover, no patient showed respiratory-chain enzyme levels below normal range. Values for activities of complexes in the PD group did not correlate with age at onset, duration, scores of the Unified Parkinson's Disease Rating scales, or Hoehn and Yahr staging. These results suggest that the presence of defects of respiratory-chain complexes could depend on methodologic aspects, and that determinations of respiratory-chain enzymes in cell homogenates are not generally appropriate for evaluating abnormal mitochondrial dysfunction, especially when the amount of the specific enzyme is relatively low, as is the case of blood cells. In addition, the method of measuring complex I activity is critical for evaluating the results. In conclusion, our finding of normal mitochondrial function in lymphocyte mitochondria suggests that this tissue cannot be used to develop a diagnostic test for PD.