Paul Maertens

ANTI-MUSK ANTIBODY AFTER THYMECTOMY IN A PREVIOUSLY SEROPOSITIVE MYASTHENIC CHILD

We report a young girl with myasthenia gravis (MG) who was first seen at age 2 for unexplained falls, diplopia, and ptosis. The patient was born as a full-term spontaneous vaginal delivery and spoke her first words and started walking at the age 10 months. The child was physically active initially and loved to play and run. At age 27 months, the patient started having difficulty rising up while she was lying or sitting. She also experienced increasing difficulty swallowing without any dyspnea. Diagnostic workup at age 2 revealed a positive neostigmine test with improved muscle strength. Electromyography showed a decrement of 20 to 28% with 3- and 10-Hz repetitive stimulation in two nerve muscle pairs; anti-acetylcholine receptor antibody (anti-AChR Ab) levels were 0.6 and 1.3 on consecutive testing (N 0 to 0.4). Chest radiograph and CT scan did not reveal any additional findings. …

Maternal-fetal transport of vitamin K1 and its effects on coagulation in premature infants

We conducted a prospective study to determine (1) the maternal-fetal vitamin K1 transport in premature infants after vitamin K1 was given to the mothers antenatally and (2) the vitamin K1 effects on blood coagulation in the babies. Women in labor at less than or equal to 34 weeks of gestation were randomly selected to receive antenatal vitamin K1, 5 mg given intramuscularly (vitamin K1 group), or no vitamin K1 (control group). Eight infants, including one set of twins, were in the vitamin K1 group and six in the control group. Vitamin K1 concentrations were higher in the vitamin K1 group than in the control group (p = 0.06). Activated partial thromboplastin time was prolonged, and factor II coagulation activity and factor II antigen were proportionately decreased in cord plasma in both groups. The average ratio of factor II coagulation activity to antigen was not decreased in either group. Protein induced by vitamin K absence-II (PIVKA-II) was not detectable in any cord plasma sample in either group. These findings support previous reports that the decreased vitamin K-dependent coagulation activity in premature infants is the result of reduced synthesis of precursor proteins, rather than the result of vitamin K deficiency, and suggest that additional vitamin K1 is not likely to improve coagulation activity. Among those infants who underwent cranial ultrasonography, all four in the vitamin K1 group and one of five in the control group had mild intraventricular hemorrhage. Studies of a larger number of patients are necessary before it can be established that maternal antenatal administration of vitamin K1 results in improvement of coagulation and the prevention of intraventricular hemorrhage in premature infants.

PONTINE CRYPTOCOCCOMA IN A NONIMMUNOCOMPROMISED INDIVIDUAL : MRI CHARACTERISTICS

The case of a pontine cryptococcoma in a nonimmunocompromised, previously healthy 16‐year‐old boy is presented. The patient had slowly progressive brainstem signs with right cranial nerves V, VII, and VIII palsies, and contralateral corticospinal and spinothalamic deficits. Magnetic resonance images (MRI) revealed, within the right pons, a 1‐cm diameter round mass lesion, hypointense on T1‐weighted images, hyperintense on T2‐ weighted images, and with rim enhancement after infusion of gadopentetate dimeglumine. This is the only report of the MRI findings in an isolated pontine cryptococcoma in an immunocompetent patien. Early recognition of this specific MRI pattern is essential, because complete recovery can be achieved with prompt antifungal treatment.

Intermediate filament protein accumulation in motor neurons derived from giant axonal neuropathy iPSCs rescued by restoration of gigaxonin

Giant axonal neuropathy (GAN) is a progressive neurodegenerative disease caused by autosomal recessive mutations in the GAN gene resulting in a loss of a ubiquitously expressed protein, gigaxonin. Gene replacement therapy is a promising strategy for treatment of the disease; however, the effectiveness and safety of gigaxonin reintroduction have not been tested in human GAN nerve cells. Here we report the derivation of induced pluripotent stem cells (iPSCs) from three GAN patients with different GAN mutations. Motor neurons differentiated from GAN iPSCs exhibit accumulation of neurofilament (NF-L) and peripherin (PRPH) protein and formation of PRPH aggregates, the key pathological phenotypes observed in patients. Introduction of gigaxonin either using a lentiviral vector or as a stable transgene resulted in normalization of NEFL and PRPH levels in GAN neurons and disappearance of PRPH aggregates. Importantly, overexpression of gigaxonin had no adverse effect on survival of GAN neurons, supporting the feasibility of gene replacement therapy. Our findings demonstrate that GAN iPSCs provide a novel model for studying human GAN neuropathologies and for the development and testing of new therapies in relevant cell types.

Cardiofaciocutaneous syndrome (CFC) with congenital peripheral neuropathy and nonorganic malnutrition : An autopsy study

Many phenotypic manifestations have been reported in cardiofaciocutaneous (CFC) syndrome, but none, to date, are pathognomonic or obligatory. Previous histopathological studies reported findings in skin and hair; no autopsy studies have been published. We report the clinical and autopsy findings of a 7‐year‐old boy with severe CFC syndrome and malnutrition of psychosocial origin. Manifestations of CFC, reported previously, included macrocephaly and macrosomia at birth; short stature; hypotonia; global developmental delays; dry, sparse thin curly hair; sparse eyebrows and eyelashes; dilated cerebral ventricles; high cranial vault; bitemporal constriction; supraorbital ridge hypoplasia; hypertelorism; ptosis; exophthalmos; depressed nasal bridge; anteverted nostrils; low‐set, posteriorly‐rotated, large, thick ears; decayed, dysplastic teeth; strabismus; hyperelastic skin; wrinkled palms; keratosis pilaris atrophicans faciei; ulerythema ophryogenes; hyperkeratosis; gastroesophageal reflux; and tracheobronchomalacia. Additional findings, not previously reported, include islet cell hyperplasia, lymphoid depletion, thymic atrophy and congenital hypertrophy of peripheral nerves with onion bulb formations. Although the islet cell hyperplasia, lymphoid depletion, and thymic atrophy are nonspecific findings that may be associated with either CFC or malnutrition, the onion bulb hypertrophy is specific for a demyelinating–remyelinating neuropathy. These findings implicate congenital peripheral neuropathy in the pathogenesis of the developmental delays, feeding difficulties, respiratory difficulties, ptosis and short stature in this case. Additional studies of other cases of CFC are needed.

A novel RSK2 (RPS6KA3) gene mutation associated with abnormal brain MRI findings in a family with coffin-lowry syndrome

Coffin–Lowry syndrome (CLS) is an X‐linked mental retardation syndrome caused by defects in the RSK2 gene. We have identified a CLS family with four patients in two generations. The patients in this family, a mother and her three children (a male and two females), all have severe mental retardation with the typical CLS phenotype. In addition, brain MRI studies on the three siblings revealed abnormalities in deep subcortical white matter, thinning of the corpus callosum, hypoplastic cerebellar vermis, and asymmetry of the lateral ventricles. The degree of severity of the MRI findings correlated with the severity of mental retardation in the patients. Extensive mutation screening was performed on the entire RSK2 gene in this family. Twenty‐two exons including the intron/exon junctions were amplified by PCR and subsequently sequenced on both strands. A novel mutation, a two‐nucleotide insertion (298 ins TG), was identified. The insertion creates a stop codon at codon 100, resulting in a 99 amino acid truncated RSK2 protein. All patients tested have the same mutation, and no other mutation could be found in the RSK2 gene from the proband. The mutation was confirmed by PCR/RFLP. X‐chromosome inactivation assay on the female patients revealed significant skewing toward inactivation of the normal RSK2 allele. Thus, this novel mutation is likely to be responsible for the unusual clinical presentation in this family, which includes full phenotypic expression in females and unique brain MRI abnormalities. The pathological function of the mutation and genotype/phenotype correlation between the mutation and this unusual clinical presentation await further clarification.

Cerebellar infarct: Late complication of the Fontan procedure?

Cardiac disease is present in approximately 30% of children with stroke. Other case reports have documented stroke in patients who have previously undergone the Fontan procedure for correction of tricuspid atresia. Most of these strokes have occurred in the immediate postoperative period. There has been one report of a cerebral infarction 3 1/2 months after surgery. We report a child with superior cerebellar artery distribution infarction after undergoing the Fontan procedure 24 months previously. Previous reports of stroke in patients having undergone the Fontan procedure and possible etiologies for these strokes are discussed. We believe our patient had the longest procedure-to-stroke interim yet reported.

Magnetic resonance imaging of mesial temporal sclerosis: case reports

Two patients with uncontrollable complex partial seizures had normal findings on pre- and postinfusion computed tomography scans. Magnetic resonance imaging demonstrated, in both patients, a lesion in the temporal lobe suggestive of mesial temporal sclerosis. One patient underwent temporal lobectomy, and the radiologic diagnosis was verified. In patients with complex partial seizures, magnetic resonance imaging appears to be able to noninvasively localize temporal lobe lesions in preparation for surgical intervention.

Infantile Lhermitte-Duclos Disease Treated Successfully With Rapamycin

Lhermitte-Duclos disease is a rare hamartomatous tumor of the cerebellum resulting from a mutation in the phosphatase and tensin homolog (PTEN) gene: it has been reported in fewer than 10 infants. Rapamycin treatment has not yet been described in Lhermitte-Duclos disease. The infant underwent shunt placement shortly after birth for aqueductal stenosis. Her clinical progression included failure to thrive, seizures, episodes of decerebrate posturing, loss of respiratory drive, and pituitary insufficiency from mass effect. The characteristic “tiger stripe” sign on imaging prompted diagnosis. Rapamycin therapy was initiated at 18 months. Within 5 months, our patient has become responsive to her surroundings and had return of spontaneous breathing. Repeat magnetic resonance imaging (MRI) reveals lack of brainstem compression or distortion of pituitary stalk. Rapamycin should be considered in cases of Lhermitte-Duclos disease where surgical removal may not be an option, as in our case where the cerebellum was entirely involved.

A new type of mitochondrial encephalomyopathy with stroke-like episodes due to cytochrome oxidase deficiency

Several clinical syndromes have been associated with cytochrome oxidase (EC 1.9.3.1) deficiency. Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) might be one such syndrome (Pavlakis et al., 1984). Here we present a patient with a progressive encephalomyopathy, stroke-like episodes and cytochrome oxidase deficiency in the biopsied skeletal muscle.