63 research outputs found
Anterior fontanelle pressure monitoring in infants
The objectives of this study were
1 To evaluate whether the R TT could be
used as a 'fontanometer'.
The literature on non-invasive ICP
measurement techniques used in infants
and children was studied to avoid problems
already encountered by others. Subsequently,
a special R TT holding device
with fixation frame was developed for the
accurate measuring of AFP.
2 To test this measuring technique in a
clinical setting AFP was established in
healthy newborns and infants and the
pressure values thus gathered were related
to the normal values reported in the
literature. Thereafter, AFP was monitored
in patients with various neurological and
pediatric diseases. The technique was tested
both during short term and long term
(continuous) measurements. The AFP recordings
themselves, were tested on their
readability by four observers by performing
an inter-observer analysis.
3 To test whether the results of AFP
measurements could have played a role in
clinical practice with respect to the question
of whether or not shunting operations should be pedormed, a retrospective study
of the patient data was undertaken.
In the following six chapters of this thesis
these objectives will be clarified. After a
historical review (chapter 2) the AFP monitoring
technique will be described (chapter
3). Normal AFP values and AFP values
in patients will be given and discussed in
12
the chapters 4 and 5 respectively. An interobserver
study of the AFP recordings
including statistical analysis procedures is
the subject of chapter 6. In chapter 7 the
role of AFP monitoring in daily clinical
practice will be viewed in the aspect of
pedorming shunting operations m
children
Novel mutations expand the clinical spectrum of DYNC1H1-associated spinal muscular atrophy
OBJECTIVE
To expand the clinical phenotype of autosomal dominant congenital spinal muscular atrophy with lower extremity predominance (SMA-LED) due to mutations in the dynein, cytoplasmic 1, heavy chain 1 (DYNC1H1) gene.
METHODS
Patients with a phenotype suggestive of a motor, non-length-dependent neuronopathy predominantly affecting the lower limbs were identified at participating neuromuscular centers and referred for targeted sequencing of DYNC1H1.
RESULTS
We report a cohort of 30 cases of SMA-LED from 16 families, carrying mutations in the tail and motor domains of DYNC1H1, including 10 novel mutations. These patients are characterized by congenital or childhood-onset lower limb wasting and weakness frequently associated with cognitive impairment. The clinical severity is variable, ranging from generalized arthrogryposis and inability to ambulate to exclusive and mild lower limb weakness. In many individuals with cognitive impairment (9/30 had cognitive impairment) who underwent brain MRI, there was an underlying structural malformation resulting in polymicrogyric appearance. The lower limb muscle MRI shows a distinctive pattern suggestive of denervation characterized by sparing and relative hypertrophy of the adductor longus and semitendinosus muscles at the thigh level, and diffuse involvement with relative sparing of the anterior-medial muscles at the calf level. Proximal muscle histopathology did not always show classic neurogenic features.
CONCLUSION
Our report expands the clinical spectrum of DYNC1H1-related SMA-LED to include generalized arthrogryposis. In addition, we report that the neurogenic peripheral pathology and the CNS neuronal migration defects are often associated, reinforcing the importance of DYNC1H1 in both central and peripheral neuronal functions
Paroxysmal exercise-induced dyskinesia and epilepsy is due to mutations in SLC2A1, encoding the glucose transporter GLUT1
Paroxysmal exercise-induced dyskinesia (PED) can occur in isolation or in association with epilepsy, but the genetic causes and pathophysiological mechanisms are still poorly understood. We performed a clinical evaluation and genetic analysis in a five-generation family with co-occurrence of PED and epilepsy (n = 39), suggesting that this combination represents a clinical entity. Based on a whole genome linkage analysis we screened SLC2A1, encoding the glucose transporter of the blood-brain-barrier, GLUT1 and identified heterozygous missense and frameshift mutations segregating in this and three other nuclear families with a similar phenotype. PED was characterized by choreoathetosis, dystonia or both, affecting mainly the legs. Predominant epileptic seizure types were primary generalized. A median CSF/blood glucose ratio of 0.52 (normal >0.60) in the patients and a reduced glucose uptake by mutated transporters compared with the wild-type as determined in Xenopus oocytes confirmed a pathogenic role of these mutations. Functional imaging studies implicated alterations in glucose metabolism in the corticostriate pathways in the pathophysiology of PED and in the frontal lobe cortex in the pathophysiology of epileptic seizures. Three patients were successfully treated with a ketogenic diet. In conclusion, co-occurring PED and epilepsy can be due to autosomal dominant heterozygous SLC2A1 mutations, expanding the phenotypic spectrum associated with GLUT1 deficiency and providing a potential new treatment option for this clinical syndrome
Sydenham's Chorea: A Practical Overview of the Current Literature
Sydenham's chorea is characterized by uncoordinated movements, emotional instability, and hypotonia. It can occur up to several months after group A beta-hemolytic Streptococcus infection. A diagnosis of Sydenham's chorea in a patient with acute chorea involves an application of the Jones criteria and the exclusion of other causes of chorea. In patients with an atypical history or hemichorea, cranial magnetic resonance imaging is indicated to exclude other cerebral pathologies. A pathogenesis has not been elucidated, and therapy has not been investigated in placebo-controlled trials. Antibiotic treatment and a 2-week or 3-week schedule of antibiotic prophylaxis are recommended. If the chorea is severe, valproate or carbamazepine can be effective. In more severely affected patients, dopamine receptor blocking agents or corticosteroids can be used. (C) 2010 by Elsevier Inc. All rights reserved.Pathophysiology of paroxysmal and chronic degenerative progressive disorder of the central and periferal nervous syste
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