Neurological deficits are associated with increased brain calcinosis, hypoperfusion, and hypometabolism in idiopathic basal ganglia calcification.

We report two familial cases of idiopathic basal ganglia calcification. A 60-year-old proband with choreoathetosis, dysarthria, and cognitive decline showed more extensive brain calcinosis, hypoperfusion, and hypometabolism than did his asymptomatic 82-year-old mother. The mother had no frontal lobe calcinosis but basal ganglia and dentate nucleus depositions were detectable. Perfusion neuroimaging, however, was normal in the asymptomatic mother and abnormal in the clinically impaired proband. The presence of calcinosis cannot be used as an index of neurological impairment but the extent of calcinosis and reduction in perfusion and metabolism may be useful for separating symptomatic from asymptomatic subjects with IBGC. These findings suggest that an interruption of neuronal circuitry may cause neurological deficits. The degree of neurological deficits may correlate with the severity of calcinosis and the reduction of perfusion and metabolism.     

McArdle's disease in two generations: autosomal recessive transmission with manifesting heterozygote

A 17-year-old boy had exercise-induced cramps and myoglobinuria. The mother had myalgia and weakness after exercise but the father was asymptomatic. Muscle biopsy was normal in the father but showed glycogen storage and absent or markedly decreased histochemical stain for phosphorylase in mother and son. Autosomal dominant McArdle's disease was considered likely, but biochemical studies showed that muscle phosphorylase activity was 0.6% of normal in the son, 20% in the mother, and 45% in the father, with corresponding decreases of cross-reacting material by immunotitration. These data suggest autosomal recessive transmission. One of the parents was clinically silent and the other was a manifesting heterozygote.     

Childhood bullying as a predictor for becoming a teenage mother in Finland

The aim of this study is to examine the association between bullying behaviour at the age of 8 and becoming a mother under the age of 20. This birth cohort study included 2,867 Finnish girls at baseline in 1989. Register-based follow-up data on births was collected until the end of 2001. Information, both on the main exposure and outcome, was available for 2,507 girls. Both bullies and victims had an increased risk of becoming a teenage mother independent of family-related risk factors. When controlled for childhood psychopathology, however, the association remained significant for bullies (OR 2.2, 95% CI 1.2–4.1) and bully-victims (OR 1.8, 95% CI 1.05–3.2), but not for pure victims. Reports of bullying and victimisation from the girls themselves, their parents and their teachers were all associated with becoming a teenage mother independent of each other. There is a predictive association between being a bully in childhood and becoming a mother in adolescence. It may be useful to target bullies for teenage pregnancy prevention.     

Acid maltase levels in muscle in heterozygous acid maltase deficiency and in non-weak and neuromuscular disease controls

Acid maltase (AM) deficiency carriers can be detected by muscle enzyme assay. The assay indicates that, just as in infantile and childhood cases, adult cases of the disease are transmitted by autosomal recessive inheritance. With the maltose hydrolysis assay, in some neuromuscular diseases, muscle AM activity can be as low as in heterozygous AM deficiency. A relatively low muscle AM activity in myxoedema myopathy is confirmed. In human muscle, the K_m of the enzyme for maltose hydrolysis is 7·2 to 9 × 10⁻³M. A modification of the enzyme assay based on this fact is recommended.     

Familial colloid cyst of the third ventricle

We describe the cases of a mother and son who presented one year apart with a colloid cyst of the third ventricle. The mother was symptomatic and had complete resolution of her symptoms after surgical intervention. Her son was asymptomatic. There have been several reported instances of a familial association of colloid cysts of the third ventricle. The probability of a colloid cyst occurring in the same family coincidentally is possible, but highly unlikely (1 x 10(10)). The increasing number of reports of the familial incidence of colloid cysts would suggest the possibility of an autosomal dominant inheritance pattern, but to date, a familial pattern of inheritance has not been recognised. If there is a potential genetic link, then screening of asymptomatic relatives may be indicated. With non-invasive imaging techniques, such as computed tomography and magnetic resonance imaging scanning, accurate diagnosis and effective elective treatment is possible. This may result in preventing future complications as a result of hydrocephalus or sudden unexpected death, and also reduce morbidity as surgery can be done electively rather than as an emergency procedure.     

Hereditary continuous muscle fiber activity

We describe a family with classic features of continuous muscle fiber activity (Isaacs-Mertens syndrome) appearing in an autosomal dominant pattern. Both a mother and her son had muscle stiffness and rigidity in early childhood. Because the mother's condition was not immediately apparent, we recommend a thorough examination of family members.     

Age-related macular degeneration is associated with probable cerebral amyloid angiopathy: A case-control study

BackgroundAge-related macular degeneration (AMD) is a common retinal degenerative disorder among older individuals. Amyloid deposits, a hallmark of cerebral amyloid angiopathy (CAA), may be involved in the pathogenesis of AMD. Since amyloid deposits may contribute to the development of both AMD and CAA, we hypothesized that patients with AMD have a higher prevalence of CAA.ObjectiveTo compare the prevalence of CAA in patients with or without AMD matched for age.MethodsWe conducted a cross-sectional, 1:1 age-matched, case-control study of patients ≥40 years of age at the Mayo Clinic who had undergone both retinal optical coherence tomography and brain MRI from 2011 to 2015. Primary dependent variables were probable CAA, superficial siderosis, and lobar and deep cerebral microbleeds (CMBs). The relationship between AMD and CAA was assessed using multivariable logistic regression and was compared across AMD severity (none vs early vs late AMD).ResultsOur analysis included 256 age-matched pairs (AMD 126, no AMD 130). Of those with AMD, 79 (30.9%) had early AMD and 47 (19.4%) had late AMD. The mean age was 75±9 years, and there was no significant difference in vascular risk factors between groups. Patients with AMD had a higher prevalence of CAA (16.7% vs 10.0%, p=0.116) and superficial siderosis (15.1% vs 6.2%, p=0.020), but not deep CMB (5.2% vs 6.2%, p=0.426), compared to those without AMD. After adjusting for covariates, having late AMD was associated with increased odds of CAA (OR 2.83, 95% CI 1.10-7.27, p=0.031) and superficial siderosis (OR 3.40, 95%CI 1.20-9.65, p=0.022), but not deep CMB (OR 0.7, 95%CI 0.14-3.51, p=0.669).ConclusionsAMD was associated with CAA and superficial siderosis but not deep CMB, consistent with the hypothesis that amyloid deposits play a role in the development of AMD. Prospective studies are needed to determine if features of AMD may serve as biomarkers for the early diagnosis of CAA.     

Immunocytochemical analysis of normal and acid maltase-deficient muscle cultures

Muscle cultures from patients with infantile and later-onset acid maltase deficiency (AMD) and from unaffected controls were studied immunocytochemically with anti-acid maltase (anti-AM) antibodies and fluorescein-labeled goat anti-rabbit IgG second antibody. In control muscle cells, an intense granular distribution of staining was seen, consistent with lysosomal localization of AM. Cultured muscle cells from two patients with infantile AMD (Pompe's disease) did not fluoresce, whereas cells from two patients with AMD of later onset did fluoresce, showing a distribution similar to that of controls.     

Understanding the Pathways between Mothers’ Childhood Maltreatment Experiences and Patterns of Insecure Attachment with Young Children via Symptoms of Depression

Although research has suggested that mothers who experienced childhood maltreatment tend to exhibit heightened risk for attachment difficulties with their young children, less is known about the mechanisms underlying this association. Thus, this study examined mothers’ symptoms of depression as a mediator in the relationship between mothers’ childhood maltreatment experiences and patterns of insecure (i.e., anxious, avoidant, and disorganized) mother–young child attachment. Mothers (N?=?146) with children aged 1½-to 5-years provided ratings of their childhood maltreatment experiences, attachment with their young children, and symptoms of depression. Mothers’ symptoms of depression mediated significantly the relationship between mothers’ childhood maltreatment experiences and patterns of insecure mother–young child attachment. These findings suggested that symptoms of depression in the context of mothers’ childhood maltreatment may be related more directly to mother–young child attachment than childhood maltreatment experiences alone. These results demonstrated the importance of promoting trauma-informed parenting interventions for facilitating secure emotional connections between mothers and their young children.     

Immunocytochemistry of muscle cytoskeletal proteins in acid maltase deficiency

Immunocytochemistry of dystrophin, spectrin, vinculin (sarcolemmaspecific proteins), and desmin (an intermediate filament protein) were investigated in 5 patients with acid maltase deficiency (AMD). One patient had infant onset, 2 had childhood onset, and 2 had adult onset. All had a vacuolar myopathy with autophagic vacuoles containing glycogen and cytoplasmic degradation products. Dystrophin, spectrin, and vinculin were localized at the sarcolemma as in normal muscle fibers. Within the cytoplasm of many fibers, immunoreactivity for the three proteins was seen as single or multiple spots or as circular structures, which most likely corresponded to the limiting membrane of vacuoles. Desmin was overexpressed at the periphery of some vacuoles. It is plausible that, before exocytosis occurs, sarcolemma-specific proteins appear within the vacuole membrane. Vacuole immunolabeling frequently occurred in the patients with childhood and adult onset AMD, but very rarely occurred in the case with infant onset. We hypothesize that a reduced exocytosis rate might explain the infrequent vacuole immunolabeling and the early onset of the infant form of the disease. © 1994 John Wiley & Sons, Inc.     

Thrombolytic therapy of acute ischemic stroke during pregnancy

The authors report eight pregnant women with acute ischemic stroke treated with thrombolysis (rt-PA [recombinant human tissue plasminogen activator] or urokinase). Seven women recovered. Two extracranial and two asymptomatic intracranial hemorrhages complicated treatment; one woman died of arterial dissection complicating angiography. Three patients had therapeutic abortions, two fetuses were miscarried, and two babies were delivered healthy. Although pregnant women may be treated safely with thrombolytics, risks and benefits to mother and fetus must be carefully weighed.     

Hypothesis regarding amyloid and zinc in the pathogenesis of Alzheimer disease: potential for preventive intervention

In Alzheimer disease (AD) the "primum movens" is amyloid (AM) production within the cerebral cortex. Cerebral AM alone may be asymptomatic. Clinical symptoms (amnesia, instrumental disorders) appear when AM induces neighboring neuritic alterations: paired hellical filaments (PHF), and distant neuronal body lesions; neurofibrillary tangles (NFT), i.e. pathologic synthesis of abnormal proteins. The timing for these inductions should be equal to the survival after the onset of amnesia: a mean of 14 months for the induction of the peri-AM neuritic alterations and a mean of 52 months for the induction of the distant to AM NFT in the hippocampic neuronal bodies. We postulate that the AM induces this neuronal pathology by producing functional zinc deficiency. The hippocampal zinc decreases in AD. The mechanism of the AM-induced zinc deficiency may be the following: the AM is formed within the walls of capillaries (senile plaques), disturbs the blood-brain barrier (BBB) and toxic metals (i.e., iron, aluminum, mercury) may enter in the cerebral cortex, where they displace the zinc in some enzymes. NFT and neuronal dysfunction may be produced by deficiency of the following zinc enzymes: (a) those of DNA metabolism, inducing abnormal DNA in the neurons and therefore abnormal protein synthesis, PHF-NFT; (b) those of glutamate (GLU) dehydrogenase (which catabolizes GLU), resulting in an excitotoxic increase of GLU; (c) those of neuronal detoxification, superoxydedismutase, carbonic anhydrase, and lactate dehydrogenase leading to neuronal toxicity. During the window between AM formation and PHF-NFT production (14-52 months), a zinc complex crossing the BBB may be useful to prevent AM of producing PHF-NFT, and also to normalize neuronal detoxification.(ABSTRACT TRUNCATED AT 250 WORDS)     

Glut1 deficiency: Inheritance pattern determined by haploinsufficiency

Two families manifesting Glut1 deficiency syndrome (DS) as an autosomal recessive trait are described. In 1 family, a severely affected boy inherited a mutated allele from his asymptomatic heterozygous mother. A de novo mutation developed in the paternal allele, producing compound heterozygosity. In another family, 2 mildly affected sisters inherited mutations from their asymptomatic heterozygous consanguineous parents. Red blood cell glucose uptake residual activity, a surrogate of haploinsufficiency, correlated with the clinical severity. These cases demonstrate that Glut1 DS may present as an autosomal recessive trait. The clinical pattern of inheritance is determined by the relative pathogenicity of the mutation and the resulting degree of haploinsufficiency. Ann Neurol 2010     

The relationship between eye-winking tics, frequent eye-blinking and blepharospasm.

A family is reported in which three generations were affected with eye-winking tics and/or blepharospasm. The proband developed eye-winking tics in childhood and then developed excessive blinking progressing to blepharospasm by the age of 21 years. His mother presented with Meige's syndrome and spasmodic torticollis at the age of 59 years; his uncle had blinked excessively from his early forties. His eldest son developed an eye-winking tic with facial grimacing at the age of 8 years, and in another son, a self-limiting period of eye-blinking occurred at the age of 4 years. The recovery cycle of the blink reflex was abnormal in all three generations. Three other children with eye-winking tics have a parent or close relative with frequent eye-blinking or blepharospasm. Five patients with adult-onset blepharospasm or Meige's syndrome are also described who had excessive eye-blinking dating back to childhood. It is suggested that eye-winking tics, frequent blinking and blepharospasm may share common pathophysiological mechanisms; the clinical expression may be age-related.     

Neuropsychological testing may predict early progression of asymptomatic adrenoleukodystrophy

OBJECTIVES: To investigate the correlation between neuropsychological and MRI findings in children with the childhood cerebral (CCALD) and asymptomatic forms of X-linked adrenoleukodystrophy (ALD) and to identify early cognitive markers that may predict disease progression in asymptomatic children with ALD. BACKGROUND: The few published neuropsychological studies on CCALD suggest a correlation between the pattern of cognitive deficit and lesion site; however, neuropsychological performance in asymptomatic children with ALD has not been investigated. METHODS: The authors assessed cognitive function and cerebral MRI findings in seven CCALD and eight asymptomatic ALD children. RESULTS: The CCALD children's cognitive skills were severely compromised, especially Wechsler and executive functions. Visual perception, short-term memory, and language were generally preserved, except that naming was severely impaired. All had extensive posterior white matter deterioration. The asymptomatic children had relatively intact neuropsychological performance, but their verbal fluency was compromised and naming severely impaired. All except one had mild white matter alterations. For all the children, the majority of neuropsychological test performance correlated significantly with extent of white matter lesions. CONCLUSIONS: The pattern of cognitive deterioration in children with CCALD and the significant correlation of neuropsychological test performance with extent of white matter lesions indicate a white matter dementia similar to that observed in adults with demyelinating diseases. The deficits found in asymptomatic children, despite their normal intelligence, suggest that careful neuropsychological investigation can identify early signs of malfunction. These may be markers of disease progression useful for selecting children for bone marrow transplant, although this will require confirmation by prospective longitudinal studies.     

Inverted fixation-off sensitivity in atypical benign partial epilepsy

Fixation-off sensitivity is an electroencephalographic phenomenon characterized by spike-and-wave discharges that only occur when central vision and fixation are eliminated. It is especially seen in children with Panayiotopoulos-type, early-onset, benign childhood occipital epilepsy or Gastaut type, late-onset, childhood occipital epilepsy. It can also be seen in eyelid myoclonia with absences, in other idiopathic generalized epilepsies, and in asymptomatic children without epilepsy. We describe a boy with atypical, benign partial epilepsy of childhood who exhibited the reverse: epileptiform activity that was suppressed by the absence of central vision or fixation, and activated by central vision or fixation.     

Late-onset acid maltase deficiency: Biochemical studies of leukocytes

The activities of acid and neutral maltase were measured in lymphocytes, granulocytes, and platelets isolated from controls and from 5 patients with late-onset acid maltase deficiency (AMD).Lymphocytes from patients had markedly decreased activity of acid maltase and elevated $\text{neutral}\text{acid}$ ratios. In granulocytes, acid maltase was also lower than in controls, but significant activity was retained at pH $\text{4:}\text{neutral}\text{acid}$ ratios were consistently elevated. Normal platelets had low acid and high neutral maltase activities: both enzyme activities varied within wide ranges and patients could not be distinguished from controls.The variable proportion of different cell types in unfractionated leukocyte preparations may yield unreliable values when used for detection of AMD. However, lymphocytes isolated from 20 ml of blood provide a readily accessible and reliable source of tissue for accurate diagnosis.     

Effects of parental relations and upbringing in troubled adolescent eating behaviors

Family relations may constitute a risk for developing eating problems. Not enough is known about parent-child relationship quality and upbringing in food situations. Self-report data from 80 high school students (45 males) showed that females had more eating problems than males, and their problems were related both to insecure mother attachment, controlling for body/weight dissatisfaction, and to more memories of childhood food rules. Secure mother attachment was related to decreased eating problems, via increasing body/weight satisfaction. Especially the mother- daughter relationship seems to affect adolescent girls' eating habits and can either protect against or enhance the risk for eating problems.     

Electroencephalographic changes and seizures in familial hemiplegic migraine patients with the CACNA1A gene S218L mutation

The S218L CACNA1A mutation has been previously described in two families with familial hemiplegic migraine. We present three siblings with the mutation with the novel association of childhood seizures, and highlight the dynamic changes seen on electroencephalography during hemiplegic migraine attacks. Depressed activity contralateral to the hemiparesis was seen on electroencephalography during acute hemiplegic migraine attacks, which may be due to changes to calcium channels caused by the S218L mutation. Both parents were asymptomatic and did not carry the S218L mutation in their blood. This suggests the presence of mosaicism in the transmitting parent.