Controversies and pitfalls in diagnosing Huntington's Disease

Huntington's disease is an inherited disorder characterised by involuntary movements, as well as psychiatric and cognitive disorders, that occur on average between the ages of 30 and 50. The diagnosis is made on the basis of the motor characteristics of the disease. The diagnostic confidence level, or the extent to which the researcher thinks that the characteristics fit the disease, is used for this. This research shows that this scale is not a reliable instrument for determining the onset of the disease. A small group develops the disease during childhood (paediatric Huntington's disease). In these children, it often takes a long time before the diagnosis is made. Interviews with parents show that although they believe that an earlier diagnosis would have been beneficial for their children, they themselves benefited from postponing the diagnosis due to grief at the loss of, or great concern for, their partner with Huntington's disease. Another group becomes ill at an older age (>60 years; late-onset Huntington's disease). These patients often experience balance problems from the outset of the disease and it is often not clear to them that Huntington's disease runs in the family. This makes it more difficult to diagnose the disease in this group. Huntington's disease is caused by an abnormal elongation in the Huntingtin gene. Repeats between normal and abnormal elongations are called intermediate. There is doubt about whether these people can develop disease symptoms. This dissertation does not find sufficient evidence to substantiate this. People who are at-risk for the disease can have their DNA tested through predictive research. Usually such a person is only seen by a clinical geneticist, but sometimes also by a neurologist. This dissertation shows that patients appreciate being seen also by a neurologist, regardless of the results

Description, Host-specificity, and Strain Selectivity of the Dinoflagellate Parasite Parvilucifera sinerae sp.nov. (Perkinsozoa)

17 pages, 7 figures, 2 tablesA new species of parasite, Parvilucifera sinerae sp. nov., isolated froma bloomof the toxic Dinoflagellate Alexandrium minutum in the harbor of Arenys de Mar (Mediterranean Sea, Spain), is described. This species is morphologically, behaviourally, and genetically (18S rDNA sequence) different from Parvilucifera infectans, until now the only species of the genus Parvilucifera to be genetically analyzed. Sequence análisis of the 18S ribosomal DNA supported P. Sinerae as a new species placed within the Perkinsozoa and close to P. infectans. Data on the seasonal occurrence of P. sinerae, its infective rates in natural and laboratory cultures, and intra-species strain-specific Resistance are presented. Life-cycle studies in field simples showed that the dinoflagellate resting zygote (restingcyst) was resistant to infection, but the mobile zygote (planozygote) orpelli clestage (temporary cyst) became infected. The effects of Light and salinity level son the growth of P. sinerae were examined, and the results showed that low salinity levels promote both sporangial germination and higher rates of infection. Our findings on this newly described parasite point to a complex host—parasite interaction and provide valuable information that leads to a reconsideration of the biological strategy to control dinoflagellate blooms by jeans of intentional parasitic infectionsThis research was funded by the EU Project SEED (GOCE-CT-2005-003875). R.I. Figueroa work is supported by a I3P contract and E. Garcés’ work is supported by a Ramon y Cajal grant, both from the Spanish Ministry of Education and SciencePeer reviewe

Severe course of Lyme neuroborreliosis in an HIV-1 positive patient; case report and review of the literature

<p>Abstract</p> <p>Background</p> <p>Lyme Neuroborreliosis (LNB) in a human immunodeficiency virus (HIV) positive patient is a rare co-infection and has only been reported four times in literature. No case of an HIV patient with a meningoencephalitis due to LNB in combination with HIV has been described to date.</p> <p>Case presentation</p> <p>A 51 year old woman previously diagnosed with HIV presented with an atypical and severe LNB. Diagnosis was made evident by several microbiological techniques. Biochemical and microbiological recovery during treatment was rapid, however after treatment the patient suffered from severe and persistent sequelae.</p> <p>Conclusions</p> <p>A clinician should consider LNB when being confronted with an HIV patient with focal encephalitis, without any history of Lyme disease or tick bites, in an endemic area. Rapid diagnosis and treatment is necessary in order to minimize severe sequelae.</p

Obsessive-Compulsive and Perseverative Behaviors in Huntington's Disease

Background: Neuropsychiatric symptoms are highly prevalent in Huntington's disease (HD). However, little is known of the prevalence and course of obsessive-compulsive behaviors (OCBs) and perseverative behaviors (PBs) during the progression of the disease. Objective: This review provides a summary of the literature on OCBs and PBs in HD gene expansion carriers (HDGECs). Methods: Pubmed databasewas searched for articles on OCBs and PBs in HD up to 2017. We used search terms, all synonyms for HD, and various terms for OCBs and PBs. Results: We found 5 case series and 11 original articles that describe a prevalence range of 5 to 52% for OCBs and up to 75% for PBs depending on disease stage and measurement scale used. Premanifest HDGECs report more OCBs compared to controls, and manifest HDGECs report a higher rate of OCBs compared to premanifest HDGECs. OCBs and PBs are associated with a longer disease duration and disease severity in manifest HDGECs, but decrease in the most advanced stages. When HDGECs come closer to estimated motor onset, the companion ratings on OCBs appear to be higher than the self-ratings of HDGECs. Conclusions: Both OCBs and PBs are characteristic neuropsychiatric features of HD. Perseveration is probably best distinguished from OCBs as it occurs without the individual's full awareness or insight into their presence (and the behavior may not be distressing). Although these behaviors are seldom distinguished, we conclude that differentiating OCBs from PBs in HD is beneficial for the management and treatment of these symptoms in HDGECs

Teaching Video NeuroImage:Improvement in Motor Development after Start of Levodopa in Tyrosine Hydroxylase Deficiency

A 7-month-old boy was referred with developmental delay and axial hypotonia (video 1). Screening for inborn errors of metabolism was negative and single nucleotide polymorphism array was normal (46,XY). Myotonic dystrophy (type 1) and spinal muscular atrophy were excluded. Whole exome sequencing yielded biallelic mutations in the tyrosine hydroxylase gene (c.698 G&gt;A, p.Arg233His and c.1211C&gt;T, p.Thr404Met). Subsequent CSF analysis revealed a significantly lowered homovanillic acid/5-hydroxyindoleacetic acid ratio, confirming tyrosine hydroxylase deficiency.1 Treatment with monotherapy levodopa resulted in profoundly improved motor development (video 1). After several weeks of treatment, the patient developed levodopa-induced dyskinesias (video 1),2 insomnia, and hyperactive behavior. All symptoms ameliorated with levodopa reduction

Diagnosing Juvenile Huntington's Disease:An Explorative Study among Caregivers of Affected Children

Objective: To investigate the reasons for the diagnostic delay of juvenile Huntington's disease patients in the Netherlands. Methods: This study uses interpretative phenomenological analysis. Eligible participants were parents and caregivers of juvenile Huntington's disease patients. Results: Eight parents were interviewed, who consulted up to four health care professionals. The diagnostic process lasted three to ten years. Parents believe that careful listening and follow-up would have improved the diagnostic process. Although they believe an earlier diagnosis would have benefited their child's wellbeing, they felt they would not have been able to cope with more grief at that time. Conclusion: The delay in diagnosis is caused by the lack of knowledge among health care professionals on the one hand, and the resistance of the parent on the other. For professionals, the advice is to personalize their advice in which a conscious doctor's delay is acceptable or even useful.Genetics of disease, diagnosis and treatmen

Lessons Learned from the Transgenic Huntington's Disease Rats

Huntington's disease (HD) is a fatal inherited disorder leading to selective neurodegeneration and neuropsychiatric symptoms. Currently, there is no treatment to slow down or to stop the disease. There is also no therapy to effectively reduce the symptoms. In the investigation of novel therapies, different animal models of Huntington's disease, varying from insects to nonhuman primates, have been created and used. Few years ago, the first transgenic rat model of HD, carrying a truncated huntingtin cDNA fragment with 51 CAG repeats under control of the native rat huntingtin promoter, was introduced. We have been using this animal model in our research and review here our experience with the behavioural, neurophysiological, and histopathological phenotype of the transgenic Huntington's disease rats with relevant literature