Polymicrogyria with dysmorphic basal ganglia? Think tubulin!

Dominant mutations in TUBB2B have been reported in patients with polymicrogyria. We further explore the phenotype associated with mutations in TUBB2B. Twenty patients with polymicrogyria (five unilateral) were tested for mutations in TUBB2B by Sanger sequencing. We identified two novel de novo mutations, c.743C>T (p.Ala248Val) and c.1139G>T (p.Arg380Leu) in exon 4 of TUBB2B in three unrelated families. Brain magnetic resonance images showed polymicrogyria involving predominantly the perisylvian regions. In addition, there was a dysmorphic appearance of the basal ganglia, thin corpus callosum, enlargement of the ventricles, thinning of the white matter and hypoplasia of pons and cerebellar vermis. This combination of associated features was absent in all 17 patients with polymicrogyria in whom no mutation was identified. This report underlines that the association of polymicrogyria with thin or absent corpus callosum, dysmorphic basal ganglia, brainstem and vermis hypoplasia is highly likely to result from mutations in TUBB2B and provides further insight in how mutations in TUBB2B affect protein function.

Reduced brain choline in homocystinuria due to remethylation defects.

OBJECTIVE: To investigate whether secondary impairment of the transmethylation pathway is a mechanism underlying the neurologic involvement in homocystinuria due to remethylation defects. METHODS: Twelve patients with neurologic disease due to remethylation defects were examined by brain magnetic resonance spectroscopic imaging ((1)H MRSI). Brain N-acetylaspartate, choline-containing compounds (Cho), and creatine (Cr) were quantified and compared to with controls. Metabolites of remethylation cycle and creatine biosynthesis pathway were measured in plasma and urine. RESULTS: MRSI revealed isolated Cho deficiency in all regions examined (mean concentration units +/- SD, patients vs controls): frontal white matter (0.051 +/- 0.010 vs 0.064 +/- 0.010; p = 0.001), lenticular nucleus (0.056 +/- 0.011 vs 0.069 +/- 0.009; p < 0.001), and thalamus (0.063 +/- 0.010 vs 0.071 +/- 0.007; p = 0.006). In contrast to controls, the Cho/Cr ratio decreased with age in patients in the three brain regions examined. Low creatine urinary excretion (p < 0.005), normal urine and plasma guanidinoacetate, and a paradoxical increase in plasma S-adenosylmethionine (p < 0.005) concentrations were observed. CONCLUSION: Patients with homocystinuria due to remethylation defects have an isolated brain choline deficiency, probably secondary to depletion of labile methyl groups produced by the transmethylation pathway. Although biochemical studies suggest mild peripheral creatine deficiency, brain creatine is in the reference range, indicating a possible compartmentation phenomenon. Paradoxical increase of S-adenosylmethionine suggests that secondary inhibition of methylases contributes to the transmethylation defect in these conditions.

Clinical significance of isolated hippocampal volume asymmetry in childhood epilepsy.

This study defines the clinical characteristics and evolution of 16 epileptic children with hippocampal asymmetry (HA) without sclerosis on MRI. The association of a positive family history of epilepsy (11/16), low incidence of febrile seizures (2/16), and benign prognosis (seizure control in monotherapy in 11/16, mean follow-up = 4.3 years, range 1 to 10) suggest a different clinical presentation than patients with mesial temporal sclerosis. Genetic studies of these mostly French Canadian families should help confirm the existence of a distinct syndrome.

The role of ultrasonography in imaging of paediatric head trauma.

Ultrasound appears to be a promising tool for assessment of the state of the dura in patients suffering from a diastatic skull fracture. Our goal is to identify patients who are at a high risk of developing the complications associated with this type of fracture as early as possible in order to keep the neurosurgical repair as simple as possible.

The role of cranial MRI in identifying patients suffering from child abuse and presenting with unexplained neurological findings.

OBJECTIVE: The aim of this study was to demonstrate the usefulness of cerebral MRI to detect possible child abuse in children with unexplained neurologic findings. METHOD: Between 1990 and 1997, 208 children were referred for suspected physical child abuse to the Child Protection Clinic of Ste-Justine Hospital, a tertiary care pediatric hospital. Among them, 39 children presented initially with neurological findings. For 27 of them, the CT Scan results prompted the diagnosis of child abuse. However, in 12 children, even if a CT-Scan was performed, the diagnosis and/or the mechanisms of the neurologic distress remained obscure. Investigation was completed with MRI study in those 12 cases. RESULTS: MRI findings were diagnostic for physical abuse in eight cases. A diagnosis of child abuse was made in two more cases by a combination of MRI and skeletal survey findings. In one case, MRI was suggestive but the diagnosis of child abuse could not be confirmed. One case was misinterpreted as normal. CONCLUSIONS: MRI is the test of choice to rule out child abuse when faced with a child presenting unexplained neurologic signs lasting for few days. The fact that MRI can better differentiate collections of different ages makes this imaging test particularly useful in identifying cases of child abuse. These results, however, always have to be integrated in a well conducted multidisciplinary clinical approach.

Transient visual symptoms as the initial manifestation of childhood adrenoleukodystrophy.

We report two patients with transient visual symptoms after an acute illness (hypoglycemia and head trauma) who went on to develop a progressive neurodegenerative disease (adrenoleukodystrophy). This report supports the suggestion that environmental factors play a role in the initial expression of the disease and reviews atypical visual manifestations of adrenoleukodystrophy. Proper diagnosis and institution of early treatment before the catastrophic deterioration typical of its natural history requires a high degree of suspicion.

Severe congenital hypopituitarism with low prolactin levels and age-dependent anterior pituitary hypoplasia: a clue to a PIT-1 mutation.

A 20-month-old boy presented with severe congenital growth hormone, thyrotropin, and prolactin deficiencies resulting from a de novo mutation of the PIT-1 gene. This form of congenital hypopituitarism should be suspected if pituitary anatomy is normal, especially if prolactin levels are low and, in boys, if the external genitalia are normal. Pituitary atrophy appears to be an age-dependent phenomenon in this condition.

Del(14)(q22.1q23.2) in a patient with anophthalmia and pituitary hypoplasia.

Only few cases with an interstitial deletion of chromosome 14 have been described so far. We report on a 21-month-old girl with an interstitial deletion of the long arm of chromosome 14, del(14)(q22.1q23.2). She presented with bilateral anophthalmia, absent left external auditory canal, facial asymmetry, microretrognathia, hypotonia, and psychomotor retardation. Skeletal X-rays showed lambdoid craniosynostosis, a very small sella turcica and cervical vertebral anomalies. Brain MRI showed the absence of the optic chiasm, an hypoplastic pituitary gland, and cortical atrophy. No cardiac or abdominal malformations were found. Two other patients with a similar deletion, (del(14)(q22.1q23) and del(14)(q22.1q22.3)), are described. Both presented with bilateral anophthalmia and absent pituitary or hypogonadism. These three cases suggest that the region 14q22 is important for eye and pituitary development. Interestingly, the human BMP-4 gene, a member of the TGF-beta superfamily, maps to 14q22-q23 and may play a role in pituitary and eye development.

MRI of the abnormal pediatric hand and wrist with plain film correlation.

Based on a pool of 24 selected cases of nontraumatic pathology of the hand and wrist in patients under the age of 18 years, collected from three pediatric hospitals, the authors have illustrated a number of congenital, inflammatory, and infectious conditions as well as tumors of bones and soft tissues, utilizing MRI with plain film correlation. Due to different MR signal characteristics, the etiology of macrodactyly may be recognized, e.g., vascular and/or fatty versus neurofibromatosis, etc. In septic arthritis, MR has shown abnormal marrow signal in adjacent bones denoting osteomyelitis, often unexpected from the plain film appearance. Tenosynovitis has a specific MR appearance: Fluid in the tendon sheath gives high signal on T2-weighted imaging. In arthritis--because of the associated hyperemia--there is definite synovial enhancement easily visible immediately after Gd-chelate injection. Gd also helps identify viable tissues postinfection as well as viable tumor tissue (versus scar or necrotic tissue) in tumors. Plain radiography is the imaging method of choice for diagnosis and differential diagnosis of most cases of bone cysts, tumors, and tumor-like conditions, e.g., simple and aneurysmal bone cysts, enchondroma, and osteoid osteoma. In the study of masses, MRI gives excellent detail regarding tumor staging and the extent of soft tissue tumors as well as the soft tissue component of bone tumors. In the hand and wrist, aneurysmal bone cysts are usually confined within a metacarpal or carpal bone, showing high signal intensity on T2-weighted imaging, often with fluid/fluid levels. If ganglion cysts are excluded, the most commonly encountered soft tissue masses are the vascular malformations. MR angiography can demonstrate the vascularity of the lesion. Some benign soft tissue lesions have a characteristic MR appearance, e.g., ganglion cysts, lipomata, and accessory muscles.

Visual agnosia with bilateral temporo-occipital brain lesions in a child with autistic disorder: a case study.

A 2-year-old boy meeting the criteria for autistic disorder was diagnosed 2 years later with a visual agnosia characterised by a combination of certain aspects of associative and apperceptive agnosia. MRI then revealed a severe encephalomalacia of the right temporal lobe and bilateral temporo-occipital areas. This association is discussed in terms of a clinical and aetiological relation between autistic disorder and visual agnosia.

Liver transplantation: review of the literature. Part 2: Vascular and biliary complications.

The first attempted human orthotopic liver transplantation, in 1963, involved a child with biliary atresia, who died on the operating table as a result of uncontrollable coagulopathy. Improvements in immunosuppression, surgical technique, medical imaging and postoperative care, as well as more stringent patient selection, have allowed the development of liver transplantation and its universal acceptance as the treatment for a variety of liver diseases. The radiologist plays a major role in the multidisciplinary transplantation team and must be familiar with each stage of orthotopic liver transplantation and its associated complications. In the first article of this series (Can Assoc Radiol J 1997;48[3]:171-178), the authors reviewed the anatomic features and current concepts relevant to orthotopic topic liver transplantation. In this, the second article, they discuss the vascular and biliary complications of the operation, and the third article will cover the medical complications.

Liver transplantation: review of the literature. Part 1: Anatomic features and current concepts.

The first attempted human orthotopic liver transplantation, in 1963, involved a child with biliary atresia, who died on the operating table as a result of uncontrollable coagulopathy. Improvements in immunosuppression, surgical technique, medical imaging and postoperative care, as well as more stringent patient selection, have allowed the development of liver transplantation and its universal acceptance as the treatment for a variety of liver diseases. The radiologist plays a major role in the multidisciplinary transplantation team and must be familiar with each stage of orthotopic liver transplantation and its associated complications. In the first article of this series, the author reviews the anatomic features and current concepts relevant to orthotopic liver transplantation. Future articles will discuss the vascular, biliary and medical complications of the operation.

Liver transplantation: review of the literature. Part 3: Medical complications.

The first attempted human orthotopic liver transplantation, in 1963, involved a child with biliary atresia, who died on the operating table as a result of uncontrollable coagulopathy. Improvements in immunosuppression, surgical technique, medical imaging and postoperative care, as well as more stringent patient selection, have allowed the development of liver transplantation and its universal acceptance as the treatment for a variety of liver diseases. The radiologist plays a major role in the multidisciplinary transplantation team and must be familiar with each stage of orthotopic liver transplantation and its associated complications. In the first article of this series (Can Assoc Radiol J 1997;48[3]: 171-178), the authors reviewed the anatomic features and current concepts relevant to orthotopic liver transplantation. In the second article (Can Assoc Radiol J 1997;48[4]: 231-242), they discussed the vascular and biliary complications of the operation. This, the third and final article in the series, covers the medical complications.

Synovial hemangioma: imaging features in eight histologically proven cases, review of the literature, and differential diagnosis.

OBJECTIVE: This study was undertaken to describe the imaging characteristics of synovial hemangioma, with the goal of improving the disappointing rate (22%) of clinical diagnosis of this condition. A review of the literature and the differential diagnosis of intra-articular lesions, including synovial osteochondromatosis and pigmented villonodular synovitis, are also presented. PATIENTS: The subjects of the study were 8 patients (4 males, 4 females; age range: 5-47 years; mean age: 19 years) with histologically confirmed synovial hemangioma involving the knee (n = 7) or wrist (n = 1). We retrospectively examined the imaging studies performed in these patients, including plain radiography (n = 8), magnetic resonance imaging (MRI; n = 4), angiography (n = 3), arthrography (n = 2), and contrast-enhanced computed tomography (CT; n = 2). RESULTS: Plain radiographs showed a soft tissue density suggesting either joint effusion or a mass in all patients. Phleboliths and bone erosions on plain films in four patients with extra-articular soft tissue involvement pointed to the correct diagnosis. Angiography, showing fine-caliber, smooth-walled vessels, contrast pooling in dilated vascular spaces, and early visualization of venous structures, was diagnostic in two patients. Neither arthrography nor CT yielded specific enough findings. MRI was consistently effective in allowing the correct diagnosis to be made preoperatively, showing an intra-articular or juxta-articular mass of intermediate signal intensity on T1-weighted images and of high signal intensity of T2- or T2*-weighted images with low-signal channels or septa within it. A fluid-fluid level was found in two patients with a cavernous-type lesion. CONCLUSION: Despite the limited nature of this study, it shows clearly that MRI is the procedure of choice whenever an intra-articular vascular lesion such as synovial hemangioma is suspected. Nonetheless, phleboliths and evidence of extra-articular extension of plain radiographs point to angiography as an effective procedure of first resort because it can be combined with embolotherapy.

Renal vein thrombosis in children: evidence of early flow recovery with Doppler US.

PURPOSE: To characterize renal arterial and venous Doppler signals in pediatric renal vein thrombosis (RVT) and to study changes in the circulation in the months following the acute event. MATERIALS AND METHODS: Ten patients with proved acute RVT (eight infants and two boys with renal allografts) were studied with serial Doppler ultrasonography (US) of the inferior vena cava and the main renal and intrarenal veins and arteries. RESULTS: The resistance index in the affected vessel was increased by 10% compared with that of the normal side in patients with unilateral RVT. Only the allografts had reversed diastolic flow. Venous flow, which was detected around the thrombus and in intrarenal veins in all native kidneys, was absent during the 1st week in the transplanted kidneys but reappeared thereafter in one. Perirenal collateral vessels were demonstrated with color Doppler US in one baby. Seven of eight native kidneys atrophied, and the allografts failed. CONCLUSION: Classic Doppler signs of RVT--absent venous flow and reversed diastolic arterial flow within the kidney--were present in only the acute phase in transplanted kidneys. These signs are unreliable in RVT of native kidneys.

Progressive noninfectious anterior vertebral fusion: MRI findings and association with a lipoma of the filum terminale in a 5-year-old girl.

Progressive noninfectious anterior vertebral fusion (PNAF) is a rare but well-defined entity of unknown cause. We report the MRI findings in a 5-year-old in whom PNAF was associated with a lipoma of the filum terminale.