Wolfram syndrome: a clinicopathologic correlation

Wolfram syndrome or DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy and deafness) is a neurodegenerative disorder characterized by diabetes mellitus and optic atrophy as well as diabetes insipidus and deafness in many cases. We report the post-mortem neuropathologic findings of a patient with Wolfram syndrome and correlate them with his clinical presentation. In the hypothalamus, neurons in the paraventricular and supraoptic nuclei were markedly decreased and minimal neurohypophyseal tissue remained in the pituitary. The pontine base and inferior olivary nucleus showed gross shrinkage and neuron loss, while the cerebellum was relatively unaffected. The visual system had moderate to marked loss of retinal ganglion neurons, commensurate loss of myelinated axons in the optic nerve, chiasm and tract, and neuron loss in the lateral geniculate nucleus but preservation of the primary visual cortex. The patient’s inner ear showed loss of the organ of Corti in the basal turn of the cochleae and mild focal atrophy of the stria vascularis. These findings correlated well with the patient’s high-frequency hearing loss. The pathologic findings correlated closely with the patient’s clinical symptoms and further support the concept of Wolfram syndrome as a neurodegenerative disorder. Our findings extend prior neuropathologic reports of Wolfram syndrome by providing contributions to our understanding of eye, inner ear and olivopontine pathology in this disease.     

Dementia. A review emphasizing clinicopathologic correlation and brain-behavior relationships

Numerous pathogenetic mechanisms may lead to the progressive loss of memory and intellectual function known as dementia. Currently, the dementias are classified according to clinicopathologic entities, although for clinical diagnosis, this introduces a degree of uncertainty. Characteristic patterns of behavior and anatomic pathology have been associated with specific clinicopathologic entities. Although somewhat simplistic, classification of the dementias as cortical vs subcortical embodies the precept that brain substrate is intimately tied to behavior. Lessons in brain-behavior relationships are reviewed for four clinicopathologic entities: Alzheimer's disease, Pick's disease, vascular dementia, and Parkinson's disease. Dementing illnesses have contributed significantly to our understanding of brain-behavior relationships. Major progress can be anticipated as diagnostic issues are resolved and biological and state-specific markers emerge.     

Unertan syndrome: review and report of four new cases

The aim of this study was to describe additional patients (n= 3) exhibiting the Unertan syndrome (UTS), resident in rural areas of Canakkale. The 8th and 9th families with the UTS, with a total of 16 members affected, have not been previously characterized. A single, non-familial case (Bayramic, Canakkale) occurred during early childhood after an infection with a high fever. Three cases of familial UTS were located in another village in Canakkale. All cases exhibited the three key symptoms of the UTS: (1) walking on all four extremities, (2) primitive language (only sounds), and (3) rudimentary intelligence. Magnetic resonance imaging showed mild vermial hypoplasia in the non-familial case, while there was cerebellar and vermial hypoplasia with a flattened cerebral cortex in the familial cases. Dexterity of the fingers was normal. The man from the latter family was fond of dragging a wooden box after fastening a string around his belt. The collective observations and clinical findings suggest two etiologies for the UTS: (1) genetic, via autosomal recessive transmission and (2) viral, likely the poliovirus affecting the cerebro-cerebellar structures. At a minimum, vermial hypoplasia is suggested to cause fully developed UTS. The subjects could stand upright and even walk bipedally, despite difficulties in balance (ataxia), but they preferred quadrupedal walking. The main difficulty with gait was maintaining a dynamic-asymmetric lateral balance and initiation of the first step during standing. Apparently, a quadrupedal gait in an adult is a developmental regression with absence of the higher control mechanisms for asymmetric lateral balance during bipedal walking. It is suggested that these individuals exhibit ancestral traits; the quadrupedal gait with rudimentary intelligence and primitive speech resulting from viral infections and/or genetic damage may cause devolution (reverse evolution), a manifestation of an experiment of nature as well as experimental studies in animal models. The results support the notion of punctuated evolution, in contrast to Darwin's theory of graded evolution. Dragging a wooden box using a string wrapped around the belt may also be an example of reverse evolution with regard to tool making, illuminating the very long-lasting period before the invention of the wheel. Herein, there has been no intent to insult or injure these individuals affected by the UTS; rather, this is an endeavor to better understand the mystery of human evolution. Go to the publisher's online edition of International Journal of Neuroscience for the following free supplemental resource: video clips.     

Joubert syndrome: review and report of seven new cases

Joubert syndrome (JS) is an autosomal-recessive disorder, characterized by hypotonia, ataxia, global developmental delay and molar tooth sign on magnetic resonance imaging. A variety of other abnormalities have been described in children with JS, including abnormal breathing, abnormal eye movements, a characteristic facial appearance, delayed language, hypersensitivity to noise, autism, ocular and oculomotor abnormalities, meningoencephaloceles, microcephaly, low-set ears, polydactyly, retinal dysplasia, kidney abnormalities (renal cysts), soft tissue tumor of the tongue, liver disease and duodenal atresia. Even within siblings the phenotype may vary, making it difficult to establish the exact clinical diagnostic boundaries of JS. We review the clinical characteristics of seven cases that fulfill the criteria of JS.     

Computerized axial tomography: clinicopathologic correlation.

Between August 1973 and April 1974 more than 750 patients had computerized axial tomography (CT) scans at the Massachusetts General Hospital. Ten brains from previously CT-scanned patients in this group were sectioned in the plane of the scan. Nearly exact correlation was found between the anatomic location and extent of intracranial lesions demonstrated by CT scan and the findings on gross and microscopic pathologic examination in cases of primary intracranial tumors, obstructive hydrocephalus, intracerebral hemorrhage, ischemic and hemorrhagic infarctions, pineal tumor, and thermal-burn encephalopathy. Determination of absorption values (mu) of 47 pathologically verified processes showed that high-absorption intracerebral hemorrhage and calcium-containing tumors are readily separable from other processes on the basis of mu values alone. However, the abnormal mu values of primary brain tumor, edema, and infarction are difficult to distinguish from those of normal spinal fluid and white matter.     

Joubert's syndrome. Presentation of two adult siblings with favorable evolution

We present the case of two siblings with Joubert's syndrome. They had breathing problems of unknown origin during the neonatal period. Their evolution has been followed-up from the first years of age until the present. They are now 26 and 22 years old, respectively. Both patients have a "borderline" mental level, are apparently normal, but have had progressive evolution and psychic and motor improvement. They can read, write and use the four operations in mathematics and can work with the computer. Both siblings are working in the familial agriculture, can play football at an elemental level with other young people of their village, and ride a bicycle and motorcycle. Both patients show normal gait and have difficulty running. Their language is normal, although somewhat slow. They perform their personal self-care that includes independent bathing, independent dressing, independent toileting and independent shaving. Their contact with other people is good. They are shy with women. They manage money. They have good social integration. One patient has bilateral strabismus and the other has unilateral ptosis.     

Ganser syndrome: a review of 15 cases.

Using the diagnostic criteria found in the literature, 15 new cases of Ganser syndrome were examined. A relationship was found between specific premorbid personality traits and severity of the syndrome; a high percentage of the sample belonged to an ethnic minority and was suspected of having symptoms of premorbid neurological pathology.     

Clinical and immunologic characteristics of melanoma-associated retinopathy syndrome: eleven new cases and a review of 51 previously published cases.

OBJECTIVE: To evaluate the signs, symptoms, and immune responses of patients with melanoma-associated retinopathy (MAR) syndrome. MATERIALS AND METHODS: We reviewed the clinical and immunologic findings of 62 MAR syndrome patients. They include 25 patients from our institution (11 not previously reported) and 37 patients reported from other institutions. RESULTS: There were 33 men and seven women (no gender information is available for the remaining 22 cases). Age at onset of the visual disturbance averaged 57.5 years (range, 30-78). Visual acuity of 20/60 or better was initially present in 82%. Fundus examination was normal in 44%, optic disc pallor was present in 23%, and retinal vessel attenuation was present in 30%. Vitreous cells were present in 30%. The latency from melanoma diagnosis to recognition of MAR syndrome averaged 3.6 years (range, 2 months to 19 years). Seven patients sustained visual improvement with various treatment regimens, especially with intravenous immunoglobulin and cytoreductive surgery (metastasectomy). Indirect immunohistochemical staining of the bipolar layer was typical, but several other retinal elements were also reactive. Tissue from a metastatic melanoma excised from one of the patients expressed antigens that reacted with antiretinal antibodies. CONCLUSION: MAR syndrome demonstrates diverse clinical and immunologic features. Treatment, especially intravenous immunoglobulin and cytoreductive surgery (metastasectomy), improves vision in some cases.     

Neurolymphomatosis: a clinicopathologic syndrome re-emerges.

We describe a patient with sensorimotor peripheral neuropathy and cranial neuropathy due to autopsy-proven neurolymphomatosis defined by infiltration of peripheral nerves by tumor cells and review the findings in 39 previously reported patients. The cause of the neuropathy is not known. The association with immune-deficient states suggests virally mediated pathogenesis, possibly a retrovirus.     

Joubert's syndrome associated with congenital ocular fibrosis and histidinemia

We describe a 16-month-old girl with Joubert's syndrome (JS), congenital ocular fibrosis, and histidinemia. Abnormal respiration, ptosis, and minimal eye movements were observed in the neonatal period. Intraoperative examination of the eyes later demonstrated severely restricted eye movements and abnormal insertions and fibrosis of the extraocular muscles. Computed tomography of the head revealed absence of the corpus callosum and brain stem. Histidine levels were elevated in the blood, urine, and cerebrospinal fluid. The patient was ataxic and developmentally delayed. To our knowledge, the association of JS with congenital ocular fibrosis has not previously been described. This report indicates that jerky eye movements are not an invariable finding in JS.     

Basal forebrain infarction. A clinicopathologic correlation

Following the repair of a ruptured anterior communicating artery aneurysm, a patient had a severe anterograde amnesia with sparing of other intellectual functions, apathy and loss of volition, altered arousal, and partial diabetes insipidus. Postmortem examination of the brain revealed bilateral destruction of the septal gray, nucleus accumbens, and nucleus of the diagonal band of Broca. Also involved in the lesion were inferior portions of the anterior limb of the internal capsule and globus pallidus. Discrete, microinfarcts were present in the paraventricular hypothalamic gray. Long-term therapy with desaminoarginine vasopressin nasal spray had no effect on the patient's neuropsychologic deficits.     

Secretory meningioma: clinicopathologic features of eight cases.

The clinical and morphological features of eight patients with meningothelial meningiomas with numerous pseudopsammoma bodies (secretory meningiomas) are presented. The six female and two male patients ranged in age from 43 to 68 years. Tumours were located at the petroclival region in two, the lateral parasellar region in two, the petrous apex in one and the sphenoid ridge in three patients. On magnetic resonance imaging, they were iso or hypointense on T1-weighted images, and hyper or isointense on T 2-weighted images. Peritumoral brain edema was absent in five cases, and was mild to moderate in three cases. Serum carcinoembryonic antigen (CEA) levels were measured preoperatively in three patients, with one having an elevated serum CEA level which re turned to normal following tumour resection. Immunohistochemical analysis on the resected tumour tissues, pseudopsammoma bodies and surrounding tumour cells were shown to be CEA-positive. Ultrastructurally, pseudopsammoma bodies were composed of granular and filamentous materials located predominantly in the intracellular lumina, which were lined by microvilli. While these morphological features of focal epithelial and secretory differentiation of tumour cells call attention to the broad spectrum of differentiation properties of meningiomas, the biological behavior of the eight tumours reported herein corresponded to those of meningiomas in general.     

Chemotherapy for pancreatic cancer: a neuroimaging clinicopathologic correlation.

This 52-year-old male without a significant medical history was receiving chemotherapy with diethylnorspermine (DENSPM), a polyamine analogue, for a partially resected pancreatic adenocarcinoma. Ten months after his initial diagnosis, he was admitted to an outside hospital for evaluation of altered mental status. Over the course of the next few days the patient developed progressive neurologic signs and symptoms including lethargy, tonic deviation of his eyes to the left, asymmetic pupils, and right-sided decerebrate posturing elicited by painful stimuli. Neuroimaging studies revealed multiple lesions scattered in the periventricular white matter, thalamus, midbrain pons, and cerebellar peduncles. The clinical and neuroimaging differential diagnoses are discussed, and postmortem neuropathologic correlation is presented.     

MPPH syndrome: two new cases

This report describes 2 additional cases of megalencephaly and perisylvian polymicrogyria with postaxial polydactyly and hydrocephalus syndrome, a recently recognized disorder of infants and young children with macrocrania, developmental delay/mental retardation, and often epilepsy. Medulloblastoma, a previously unreported feature in megalencephaly and perisylvian polymicrogyria with postaxial polydactyly and hydrocephalus syndrome, developed in one child at 3 years of age. Although the disorder is presumed to be genetic, the cause of megalencephaly and perisylvian polymicrogyria with postaxial polydactyly and hydrocephalus syndrome has not yet been determined.     

Antley-Bixler syndrome Description of two new cases and a review of the literature

Antley-Bixler syndrome was first described in 1975, and to date 20 cases have been reported. In addition to brachycephaly, the syndrome is associated with midface hypoplasia, often with choanal stenosis or atresia, bilateral radiohumeral synostosis, multiple joint contractures, femoral bowing and long bone fractures, ``pear-shaped' nose, dysplastic ears and, occasionally, urogenital or cardiac defects. Survival is closely linked to upper airway obstruction. This, in addition to craniosynostosis, also affects mental prognosis. The cluster of malformations and their severity are variable, and while numerous children have died early from respiratory distress, one third of them are alive and have had quite satisfactory development. With early and effective prevention of respiratory complications and early treatment of craniosynostosis, the overall prognosis can be favorable. The mode of inheritance is probably autosomal recessive, and midtrimester prenatal diagnosis is feasible. Genetic counseling depends on accurate prognostic and therapeutic data. We describe two new cases, a 4-year-old boy with unilateral coronal synostosis and radio-humeral synostosis on the same side and an 18-month-old girl with brachycephaly and imperforate anus. Received: 30 October 1996     

Ataxic hemiparesis syndrome: clinical and CT study of 20 new cases and review of the literature

20 new cases of ataxic hemiparesis syndrome (AHS) are reported and the findings compared with those of published cases. AHS may be due to lesions either of the brainstem or of supratentorial structures, where motor fibers run together with the cerebro-cerebellar pathways. Specific syndromes related to the lesion site cannot be identified from the clinical signs. Ischemic infarct is the most frequent cause of the syndrome, but hemorrhagic, neoplastic and demyelinating lesions have also been reported.

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Sommario Venti nuovi casi di emiparesi atassica sono stati osservati e confrontati con casi della letteratura. L'emiparesi atassica può conseguire a lesioni del tronco cerebrale o delle strutture sovratentoriali laddove le fibre motorie decorrono insieme alle vie cerebro-cerebellari. I quadri clinici osservati non consentono pertanto di identificare specifiche sindromi caratterizzate da danni anatomici comuni. Per quanto l'infarto ischemico ne sia di gran lunga la causa più frequente, l'emiparesi atassica è riportata anche in presenza di lesioni emorragiche, neoplastiche e demielinizzanti.

     

Episodic paroxysmal hemicrania: two new cases and a literature review.

Episodic paroxysmal hemicrania (EPH) is a rare disorder characterized by discrete bouts of hemicranial headache separated by headache-free remissions. Although EPH resembles episodic cluster headache in the location and quality of pain as well as the pattern of associated autonomic features, it is distinguished by the greater frequency and shorter duration of individual headaches. Differentiation of these disorders is important because EPH almost invariably responds to treatment with indomethacin but not to standard cluster headache therapy.