Family History Of Neurological Disease Research Articles

Deleterious Variants of FIG4, a Phosphoinositide Phosphatase, in Patients with ALS

Mutations of the lipid phosphatase FIG4 that regulates PI(3,5)P(2) are responsible for the recessive peripheral-nerve disorder CMT4J. We now describe nonsynonymous variants of FIG4 in 2% (9/473) of patients with amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS). Heterozygosity for a deleterious allele of FIG4 appears to be a risk factor for ALS and PLS, extending the list of known ALS genes and increasing the clinical spectrum of FIG4-related diseases.

Cerebral amyloid angiopathy with co-localization of prion protein and beta-amyloid in an 85-year-old patient with sporadic Creutzfeldt–Jakob disease

We report on an 85-year-old woman with hypertensive cerebral arteriolosclerosis who presented with rapidly progressive encephalopathy leading to death within 4 months. Magnetic resonance imaging showed mild cortical atrophy consistent with her age and diffuse leukoaraiosis. Her CSF 14-3-3 protein was positive. Neuropathology showed severe spongiform change and gliosis in the grey matter and immunohistochemistry revealed diffuse prion protein deposition in a predominant synaptic pattern. She had no family history of neurological disorder and genotyping did not show any prion protein gene mutation, in keeping with a diagnosis of sporadic Creutzfeldt-Jakob disease. There was also diffuse amyloid angiopathy involving the cortical and leptomeningeal arterioles of the cerebral hemispheres and cerebellum and the capillaries of the grey matter. The amyloid angiopathy expressed beta-amyloid but also prion protein and double immunostaining confirmed co-localization of both proteins in many vessel walls. Alzheimer's type pathology was restricted to a few diffuse beta-amyloid plaques in the entorhinal cortex and rare tangles in the hippocampus. Deposition of prion protein in cerebral vessels has been reported in a single case of stop codon 145 mutation of the PRNP gene. Co-localization of beta-amyloid and prion protein in the same amyloid plaque has been described in elderly patients with Creutzfeldt-Jakob or Gerstmann-Sträussler-Scheinker diseases but only exceptionally in cerebral amyloid angiopathy. In this patient, hypertensive cerebrovascular disease may have contributed to the failure to eliminate both proteins from the brain.

Neurogenic Orthostatic Hypotension

615 A 65-year-old man reports a 6-month history of dizziness, light-headedness, weakness, and fatigue while upright. He takes no medication and has no personal or family history of neurologic disease. On physical examination, his supine blood pressure is 160/100 mm Hg, with a heart rate of 72 beats per minute; on standing, his blood pressure falls to 70/40 mm Hg, with no change in heart rate. The results of the remainder of the examination, including neurologic examination, are normal. How should he be evaluated and treated?

Neurogenic Orthostatic Hypotension

A 65-year-old man reports a 6-month history of dizziness, light-headedness, weakness, and fatigue while upright. He takes no medication and has no personal or family history of neurologic disease. On physical examination, his supine blood pressure is 160/100 mm Hg, with a heart rate of 72 beats per minute; on standing, his blood pressure falls to 70/40 mm Hg, with no change in heart rate. The results of the remainder of the examination, including neurologic examination, are normal. How should he be evaluated and treated?

Iatrogenic Creutzfeldt–Jakob disease 22 years after human growth hormone therapy: clinical and radiological features

Creutzfeldt–Jakob disease (CJD) is a human transmissible spongiform encephalopathy or prion disease. Although CJD is most frequently sporadic, numerous acquired or iatrogenic CJD (iCJD) cases have been reported, about half...

Influencing factors of colostrum exposure to low-level lead and their relationship with early neural development of infants

Background Exposure to low-level lead has a toxic effect on the development of neonates, which has attracted wide attention. Colostrum lead level can be used as the indication of lead exposure. Objective To observe the relationship of colostrum lead level and the neurobehavioral development of infants. Design A prospective control observation. Setting Center for Maternal and Child Health, Shanxi Provincial Children's Hospital. Participants Totally 128 neonates of full-term normal delivery, 76 male and 52 female, from Shanxi Provincial Maternal and Child Health Center and Jiexiu Maternal and Child Health Center were involved in this study. All the involved neonates had no peripartal ischemic/hypoxic history or fetus intrauterine developmental lag. Pregnant women had no various acute and chronic diseases in pregnancy, family history of neurological disease or occupational lead exposure. 128 portions of colostrum sample of full-term normal delivery were collected. Informed consents of detected items were obtained from the puerperants and their relatives. Methods ▪ Experimental grouping: Lead level in the colostrum was determined by atomic absorption spectrometry. According to lead level in the colostrum, the neonates were classified into two exposure groups of greater than or equal to 0.24 μmol/L in a high-level lead group and less than 0.24 μmol/L in a low-level lead group. ▪ Experimental evaluation: Mental developmental index (MDI) and psychological developmental index (PDI) of 3-month-old infants were evaluated with Bayley Scales of Infant Development (BSID). The relationships of MDI, PDI and colostrum lead level were performed correlation regression analysis; The relationship of colostrum lead level and development was performed multi-factor analysis with family environment and health questionnaires. Main outcome measures ▪ Evaluation results of MDI and PDI. ▪ Multi-factor analysis results. Results Totally 128 neonates were involved in the study. Ten and eleven neonates were lost due to emigration in the high-level lead group and low-level lead group respectively, and the other 107 neonates participated in the final analysis. ▪ MDI and PDI in the high-level lead group were significantly lower than those in the low-level lead group, respectively ( P < 0.01); Regression analysis results showed that two developmental indexes were statistically negatively correlated with colostrum lead level (regression equation y = 1.9+0.01 x 1,–0.04 x 2,+0.04 x 3,+0.03 x 4). ▪ Four variables of the factors included by family environment and health questionnaires were taken into equation. Large maternal age, irrational dietary pattern in pregnancy and pollution degree of habitation environment in pregnancy were the risk factors of colostrum lead level (partial regression coefficien t =0.598 4,0.426 8,0.306 7, P < 0.05–0.01), and calcium supplementation in pregnancy was a protective factor (partial regression coefficien t =–0.455 8, P < 0.01). Conclusion High colostrum lead level will have adverse effects on the early development of neonates; Large maternal age, irrational dietary pattern in pregnancy and pollution degree of habitation environment in pregnancy are the risk factors of colostrum lead level, and calcium supplementation in pregnancy was a protective factor.

A 16-year-old girl with progressive weakness of the left leg

The patient first noted problems in 1996, almost 3 years prior to evaluation. She had fallen and injured her right knee on a brick. The onset of her left lower extremity problems was uncertain, but she noticed gradual weakness of her left foot subsequent to the injury. In January 1999, the weakness of the left foot was noted to be definite. Her left foot would slap with walking, and her mother would encourage her to “pick up her foot” when she walked. Her grandmother noted that she would often scuff her left foot. The patient experienced no pain with the weakness, and she herself was only aware of it while trying to run. The patient felt she had been unable to run properly for the last 2 to 3 years. Approximately 4 months later, electromyography (EMG) was done at Mayo Clinic at the request of the referring physician (table 1). This showed absent left peroneal motor and sensory responses and absent left sural sensory response. The left tibial motor conduction was normal. Needle examination revealed fibrillation potentials in the tibialis anterior with markedly reduced recruitment in the left peroneal innervated muscles. She was fitted with an orthosis at the local institution to prevent foot drop. View this table: Table 1 Electromyography 1999 In June 1999 at age 12, she was assessed clinically at the Mayo Clinic. She was on no medications. She had no significant past medical history but was overweight. She was born weighing 8 lbs 8 oz at normal gestation without any complications. Development was otherwise normal. She had no known exposure to any toxins and had no history of exposure to alcohol, cigarette smoking, or illicit drug use. There was no known family history of neurologic disease. The patient’s maternal grandmother had “hammer toes.” Her sister had surgically corrected femoral …

Lead level in foremilk and neurobehavioral development of neonates

Background Recently, it has been reported that blood lead level lower than 24 μmol/L can lead to learning and cognitive deficits. Objective To investigate the relationship of lead level in foremilk and early neurobehavioral development of neonates taking lead level in foremilk as lead exposure index. Design A controlled observation. Setting Maternal and Child Health Center, Shanxi Children's Hospital. Participants Totally 128 neonates of full-term normal delivery, 76 male and 52 female, from Shanxi Provincial Maternal and Child Health Center and Jiexiu Maternal and Child Health Center were involved in this study. All the involved neonates had no peripartal ischemic/hypoxic history. The corresponding puerperants were aged (27±5)years. They had no various acute and chronic diseases during pregnancy, and family history of neurological disease as well as occupational lead exposure. Informed consents of detected items were obtained from the puerperants. Methods ▪ Determination of lead level in foremilk: Altogether 128 foremilk samples, 1 mL each, were collected between January and February 2005. The same amount of violet acid was added to each sample. After foremilk was fully dissolved, 0.2 mL solution was taken for determining lead level with atomic absorption spectrometer in graphite stove. The determined process strictly followed the internal quantity control of laboratory and was involved in the blind quality control of Institute of Environmental Health of Chinese Academy. ▪ Participants grouping: Totally 128 neonates were involved, and the normal reference value of lead level of foremilk was 0.06–0.48 μmol/L. The involved neonates were assigned into high-level lead group (≥ 0.24 μmol/L, n =60) and low-level lead group (< 0.24 μmol/L, n =68). ▪ Assessment of neurobehavioral development of neonates: Neurobehavioral development level of neonates who was born 24 to 72 hours was assessed with 20-item neonatal neurobehavioral determination method, which involved behavioral ability (6 items), passive muscular tension (4 items), active muscular tension (4 items), primitive reflection (3 items) and general evaluation (3 items). Each above-mentioned scoring had 3 scales (0,1 and 2 points). The full mark of 20 items was 40 points. Neurological behaviors of neonates might be unabnormal when scoring was < 35 points. Main outcome measures Assessment results of neurobehavioral development of neonates in high- and low-level lead neonates. Results After lead-level determination, the involved neonates in two groups participated in the final analysis. Neurobehavioral total scores of neonates of high-level lead group were lower than those in the low-level lead group [(35.9±1.3) points vs.(37.7±1.4) points, P < 0.01]. The scores of neonatal erection in high-level lead group were lower than those in low-level lead group [(1.4±0.4) points vs.(1.8±0.5) points, P <0.01], and time for head erection of neonates in the high-level lead group was shortened as compared with that in the low-level lead group [(1.8±1.7) minutes vs. (3.3±2.2) minutes, P < 0.01]. Conclusion 0.24 μmol/L lead level in foremilk has certain relationship with neurobehavioral development. The main influenced manifestations are shortened duration of neonatal head erection and actively contracted extensor, i.e. cervical curved ability is weakened.

Familial cerebral cavernous haemangioma diagnosed in an infant with a rapidly growing cerebral lesion

Cavernous haemangiomas of the central nervous system are vascular malformations best imaged by MRI. They may present at any age, but to our knowledge only 39 cases in the first year of life have previously been reported. A familial form has been described and some of the underlying genetic mutations have recently been discovered. We present the clinical features and serial MRI findings of an 8-week-old boy who presented with subacute intracranial haemorrhage followed by rapid growth of a surgically proven cavernous haemangioma, mimicking a tumour. He also developed new lesions. A strong family history of neurological disease was elucidated. A familial form of cavernous haemangioma was confirmed by identification of a KRIT 1 gene mutation and cavernous haemangiomas in the patient and other family members. We stress the importance of considering cavernous haemangiomas in the context of intracerebral haemorrhage and in the differential diagnosis of rapidly growing lesions in this age group. The family history is also important in screening for familial disease.

Autophagic vacuolar myopathy in twin girls

Hereditary autophagic vacuolar myopathy (AVM) may occur in several diseases including the rimmed vacuolar myopathies, acid maltase deficiency, Danon disease, infantile autophagic vacuolar myopathy and X-linked myopathy with excessive autophagy (XMEA). In the latter three conditions the vacuoles are lined by membranes with sarcolemmal features. We present two unusual cases of autophagic vacuolar myopathy in twin girls born at term with no family history of neurological disease. After initial normal developmental milestones they developed progressive leg weakness and wasting with contractures from the age of 12 years. Investigations showed raised CK, normal female karyotype, normal acid maltase activity, normal nerve conduction and myopathic EMG features. Frozen sections of skeletal muscle were stained using routine tinctorial and histochemical methods. Immunohistochemical staining for spectrin, merosin, dystrophin, complement membrane attack complex and sarcoglycans was performed and ultrastructural examination undertaken. Direct sequence analysis of the lamp-2 gene using genomic DNA extracted from lymphocytes was performed. Histological analysis of the muscle biopsies demonstrated myofibres with vacuoles lacking glycogen and lipid many of which were delineated using immunohistochemistry for merosin, dystrophin and sarcoglycans. Ultrastructural examination showed duplication of the myofibre basal lamina with associated autophagic material. Vacuoles within myofibres were either membrane bound containing autophagic material or lined by plasma membrane and basal lamina. Intermyofibrillar glycogen was increased. Sequence analysis of the coding region and intron/exon boundaries of the lamp-2 gene was normal. This is the first report of female cases of AVM with sarcolemmal features. We suggest that these patients may represent manifesting carriers of XMEA, or alternatively, a new form of disease with a similar phenotype having autosomal recessive inheritance.

Epileptic Seizures Superimposed on Catatonic Stupor

Some patients with nonconvulsive status epilepticus are known to exhibit catatonic stupor. Thus it is necessary to rule out ictal catatonia by electroencephalography in patients with catatonic stupor. However, few reports are available on epileptic seizures superimposed on catatonic stupor. We report three cases of epileptic seizures superimposed on psychiatric catatonic stupor without a prominent predisposing factor, including high fever or encephalitis. None of the patients had a personal or family history of neurologic disease, including epilepsy. In all three patients, catatonic stupor persisted after resolution of the epileptic seizures with administration of phenytoin. In two of the three patients, catatonic stupor resolved with electroconvulsive therapy, which caused no marked adverse effects. Because it is possible that catatonic stupor itself predisposes patients to the development of epileptic seizures, electroencephalographic examinations in patients with catatonic stupor are indispensable for early recognition not only of nonconvulsive status epilepticus but also of epileptic seizures superimposed on catatonic stupor. Electroconvulsive therapy deserves consideration when catatonic stupor persists after resolution of epileptic seizures.

Evaluation of clinical diagnostic criteria for psychogenic movement disorders

Previous studies showed that there are certain features suggestive of a psychogenic disorder, and Fahn and Williams proposed criteria for psychogenic movement disorders. Data on the sensitivity and specificity of these criteria are lacking. We expanded on the Fahn and Williams criteria to create a new set of diagnostic criteria. We retrospectively reviewed 79 patients in a movement disorders specialty clinic. We applied the proposed diagnostic criteria to both cases and controls and analyzed sensitivity and specificity. The diagnostic criteria correctly identified "clinically probable" (or better) psychogenic movement disorders with a sensitivity of 83% and specificity of 100%. For "clinically possible" or greater, sensitivity was 97% and specificity was 96%. In addition, a significantly higher proportion of patients with psychogenic disease were female and reported either a family history of neurological disease or other exposure to neurological disease (P = 0.001 and 0.01, respectively). The diagnostic criteria are simple to apply and have high sensitivity and specificity for psychogenic movement disorders. Also, we report a correlation between previous exposure to a disease model and psychogenic disease.

Hirayama disease associated with a severe rhythmic movement disorder involving neck flexions

Hirayama disease is a cervical myelopathy with teenage onset of unilateral or asymmetric weakness and atrophy of intrinsic hand and forearm muscles. It is initially progressive for several years but eventually stabilizes.1,2 Its pathophysiology is still debated: Most authors report evidence of dynamic cord compression during neck flexion,1–4 but others disagree with this terminology.5 We report on a 10-year-old girl with Hirayama disease who, since infancy, had had a severe and persistent nocturnal rhythmic movement disorder with extreme repeated neck flexions caused by body and head rocking in a prone position. The girl had a 10-month history of difficulty using her left hand while playing the clarinet and performing gymnastics, increasing when her hand was cold. She had no history of trauma, pain, paresthesias, or symptoms referring to the lower extremities and no family history of neurologic disease. On examination, she was a prepubertal girl with height in …

Renal Angiomyolipoma Associated with Rapid Enlargment and Inferior Vena Caval Tumor Thrombus

No AccessJournal of UrologyCLINICAL UROLOGY: Case Reports1 Sep 2003Renal Angiomyolipoma Associated with Rapid Enlargment and Inferior Vena Caval Tumor Thrombus XAVIER GAMÉ, MICHEL SOULIÉ, SIDI MOUSSOUNI, DANIEL ROUX, GHISLAINE ESCOURROU, CHRISTINE CHEVREAU, and RICHARD AZIZA XAVIER GAMÉXAVIER GAMÉ More articles by this author , MICHEL SOULIÉMICHEL SOULIÉ More articles by this author , SIDI MOUSSOUNISIDI MOUSSOUNI More articles by this author , DANIEL ROUXDANIEL ROUX More articles by this author , GHISLAINE ESCOURROUGHISLAINE ESCOURROU More articles by this author , CHRISTINE CHEVREAUCHRISTINE CHEVREAU More articles by this author , and RICHARD AZIZARICHARD AZIZA More articles by this author View All Author Informationhttps://doi.org/10.1097/01.ju.0000074709.64318.5cAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "Renal Angiomyolipoma Associated with Rapid Enlargment and Inferior Vena Caval Tumor Thrombus." The Journal of Urology, 170(3), pp. 918–919 References 1 : Benign angiomyolipoma involving the renal vein and vena cava as a tumor thrombus: case report. J Urol1995; 153: 1205. Link, Google Scholar 2 : Renal angiomyolipoma: optimal treatment based on size and symptoms. Clin Nephrol1998; 49: 281. Google Scholar 3 : Stratégie diagnostique et thérapeutique des angiomyolipomes. Prog Urol2002; 12: 108. Google Scholar From the Departments of Urology (XG, MS, DR), Radiology (SM, RA) and Pathology (GE), Rangueil University Hospital and Department of Oncology, Claudius Regaud Institute (CC), Toulouse, France© 2003 by American Urological Association, Inc.FiguresReferencesRelatedDetails Volume 170Issue 3September 2003Page: 918-919 Advertisement Copyright & Permissions© 2003 by American Urological Association, Inc.Keywordsthrombosiskidney neoplasmsangiomyolipomaMetricsAuthor Information XAVIER GAMÉ More articles by this author MICHEL SOULIÉ More articles by this author SIDI MOUSSOUNI More articles by this author DANIEL ROUX More articles by this author GHISLAINE ESCOURROU More articles by this author CHRISTINE CHEVREAU More articles by this author RICHARD AZIZA More articles by this author Expand All Advertisement PDF DownloadLoading ...

De novo expansion of a CAG repeat in a Japanese patient with sporadic Huntington’s disease

A 49-year-old man was admitted to our hospital complaining of dysarthria and involuntary movements of his neck and extremities. He had first begun to experience involuntary neck movements at the age of 40 and his symptoms gradually progressed thereafter. There was no family history of neurological disorders. On admission he showed memory disturbance, dysarthria, and choreic movements. The involuntary movements affected his face, neck, trunk, and extremities. MRI of the brain revealed atrophy of both the cerebral cortex and the head of the caudate nucleus. DNA samples for molecular analysis were obtained from the patient and both of his parents. In this pedigree, the father carried a premutated allele of 35 CAG repeats and transmitted an expanded allele of 43 CAG repeats to his son. Paternity and maternity were analyzed using a microsatellite marker located in a different chromosome. To our knowledge, this is the first report of a sporadic case of Huntington’s disease in a non-caucasian population in which the disease prevalence is much lower than that in the caucasian population. A new mutation in the current Japanese population which shares the same mechanism as de novo mutation in Caucasians may have contributed to the frequency of HD in Japan at the present time.

Creutzfeldt–Jakob disease with a novel four extra-repeat insertional mutation in the PrP gene

To investigate the role of a short insertional mutation in the prion protein (PrP) gene (PRNP) in prion disease pathogenesis. The genetic forms of Creutzfeldt-Jakob disease (CJD) are associated with point or insertional mutations in PRNP. Whereas patients with five, six, seven, eight, and nine extra octapeptide repeats show an autosomal dominant pattern of inheritance and features of CJD, Gerstmann-Sträussler-Scheinker disease, or atypical dementia, patients with one, two, or four extra repeats have typical CJD and lack a family history of neurologic disorder. A genetic, neuropathologic, and biochemical study was carried out in a 65-year-old patient with clinical features of sporadic CJD. A novel four extra-repeat insertional mutation of PRNP was found in the patient and in his 59-year-old healthy sister. The patient showed spongiosis, nerve cell loss, and gliosis associated with diffuse PrP immunoreactivity in the cerebral cortex, subcortical gray structures, and cerebellum. A peculiar aspect was the presence of focal PrP deposits in the basal ganglia and hypothalamus, superimposed to diffuse PrP immunoreactivity. The biochemical analysis revealed that both mutant and wild-type PrP participated in the pathologic process, and that the protease-resistant core of the altered PrP isoforms was distinct from that observed in sporadic, acquired, and other genetic forms of CJD. These findings support the view that the four extra-repeat insertion in PRNP is a pathogenic mutation with low penetrance rather than a benign polymorphism, and suggest that this mutation results in the formation of a distinct PrP conformer.

La neuropathie héréditaire avec paralysie à la pression chez l'enfant : diagnostic clinique et biologique. À propos d'un cas

HNPP occurs rarely but not exceptionally during childhood. José M., seven years old, presented an isolated radial nerve palsy of progressive onset with no other clinical feature. There was no family history of neurological disorder. The electromyogram (EMG) showed a 'mosaic-like' pattern of extended sensitive and motor alterations, with diminished conduction velocities and amplitudes and increased distal latencies. HNPP was considered through the association of an isolated radial nerve palsy with an asymptomatic polyneuropathy, and was confirmed by molecular biology. HNPP is generally considered on clinical features, heredity and EMG findings. Molecular biology confirms the diagnosis in most of the cases, even in apparently sporadic patients, and is of great interest in atypical cases.

Antepartum risk factors for newborn encephalopathy: the Western Australian case-control study

Objective: To ascertain antepartum predictors of newborn encephalopathy in term infants.Design: Population based, unmatched case-control study.Setting: Metropolitan area of Western Australia, June 1993 to September 1995.Subjects: All 164 term infants...

Kufs' disease presenting as late-onset epilepsia partialis continua

A 64-year-old woman, who had no personal or family history of neurologic diseases, had an 18-month history of epilepsia partialis continua (EPC) associated with a moderate intellectual deterioration and subtle extrapyramidal rigidity. There was no photosensitive response. A thorough laboratory investigation was unremarkable. A biopsy of the rectal mucosa revealed abundant fingerprint profiles diagnostic of Kufs' disease (KD). Our case expands the clinical picture of KD and suggests that such a diagnosis should be considered in adult-onset EPC.

A progressive neurodegenerative disorder with cortical spongiform change and white matter damage presenting with pseudobulbar palsy

An autopsy case of spongiform encephalopathy with severe white matter degeneration, beginning with slowly progressive pseudobulbar palsy was reported. A 58‐year‐old man with no family history of neurologic disease noticed speech disturbance at age 38, which gradually deteriorated. By the age of 41, he became totally aphonic, but he could write and understand the meaning of writing. At age 42, he showed pseudobulbar palsy. At age 43, he gradually developed parkinsonism and generalized hyper‐reflexia. At age 46, he showed dementia, aphonia, rigidity, generalized hyper‐reflexia, left grasping, and quadriplegia in flexion. He died of respiratory failure at age 58, in the state of akinetic mutism, 20 years after the onset of the symptoms. Neuropathologically, the brain showed marked diffuse atrophy. Microscopic examination revealed spongiform encephalopathy with severe neuronal loss and profound white matter degeneration throughout the cerebrum. This case was difficult to categorize in any known neurodegenerative disease, both clinically and neuropathologically, suggesting a new entity of neurodegenerative disease.