Ependyma-lined cysts.

Ependyma-lined cystic lesions of the subarachnoid space are uncommon. They form a histologically heterogeneous group and have been referred to as epithelial, ependymal, glioependymal and neuroepithelial cysts depending on their respective histological characteristics. In this report, we describe two cases of ependyma-lined cysts in the posterior fossa that support a common pathogenesis for this diverse group of lesions.

Melanotic craniopharyngioma: a report of two cases.

We report a 74-year-old woman and a 50-year-old woman with similar histories of headache and visual disturbance who were found to have adamantinomatous craniopharyngiomas which contained melanin pigment. This finding was confirmed by the Masson Fontana method and ultrastructural studies. These are only the second and third cases reported describing melanin pigment within a craniopharyngioma. The finding of melanin in craniopharyngiomas attests to their similarities with odontogenic tumors of the jaw, which can also contain melanin pigment and also supports the hypothesis that the histogenesis of these neoplasms derives from the vestiges of Rathke's pouch epithelium.

Massive leptomeningeal amyloidosis associated with a Val30Met transthyretin gene.

We report a 69-year-old woman of Mexican origin with a 6-year history of progressive paresis, mild peripheral neuropathy, and recent onset of fluctuating mental status. Head and spinal MRI revealed contrast enhancing thickened meninges which on biopsy disclosed amyloid deposition. Immunohistochemistry identified the amyloid as transthyretin (TTR), and polymerase chain reaction/restriction fragment length polymorphism analysis of blood revealed a Val30Met mutation in one of her TTR genes. This mutation causes familial (hereditary) amyloidotic polyneuropathy of the Portuguese type (FAP 1). However, unlike FAP 1, in which peripheral neuropathy is a dominant feature, our patient's clinical manifestations, which included communicating hydrocephalus and myelopathy, were more suggestive of familial oculoleptomeningeal amyloidosis (FOLMA). In summary, the clinical presentation of TTR Met 30 mutation is more varied than previously suspected, and leptomeningeal amyloidosis should be considered in the differential diagnosis of obscure conditions involving meninges.

Concomitant branching enzyme and phosphorylase deficiencies. An unusual glycogenosis with extensive neuronal polyglucosan storage.

A baby girl was born hypotonic and was respirator-dependent until death at 43 days of age. A muscle biopsy revealed PAS-positive, diastase-resistant sarcoplasmic inclusions with a vaguely fibrillar structure by electron microscopy. Biochemical studies at autopsy disclosed complete absence of branching enzyme in skeletal muscle and heart, and a deficiency of phosphorylase activity in skeletal muscle with a modest reduction in myocardium. Storage material was present in glia and perikarya of neurons, increasing in amount in the rostrocaudal direction, involving most severely the motor neurons in the brain stem and spinal cord, dorsal root ganglia and myenteric plexi. Inclusions were also present in most organs, especially liver and skeletal muscle. Ultrastructurally, the inclusions ranged from granular aggregates of membrane-bound material concentrated in the region of Golgi apparatus to large filamentous bodies similar to polyglucosan bodies. This baby differs from other patients with infantile glycogenosis IV by the severity and onset of symptoms at birth, involvement of neuronal perikarya and widespread extraneural deposits. The combined deficiencies of branching enzyme and phosphorylase may have accounted for the unique clinical and neuropathological findings.

L-tryptophan and the eosinophilia-myalgia syndrome: pathologic findings in eight patients.

Pathologic findings in eight patients with the eosinophilia-myalgia syndrome, secondary to L-tryptophan ingestion, are reported. Tissue was obtained by biopsy alone in six patients, by biopsy and autopsy in the seventh patient, and by autopsy alone in the eighth patient. Muscle biopsies in five patients demonstrated an inflammatory infiltrate composed predominantly of lymphocytes, histiocytes, plasma cells, and a few eosinophils. The inflammation involved the perimysial and epimysial connective tissue, the walls of some small blood vessels, the perineurium of small nerve twigs, muscle spindles, and fibrous septae of subcutaneous adipose tissue. In two patients with peripheral neuropathy and one patient without overt neuropathy, denervation atrophy of muscle and perimysial and epimysial fibrosis were present. Sural nerve biopsy tissue taken from two patients displayed prominent axonopathy in one, and minimal changes in the second. Pulmonary changes in the two autopsied patients included endothelial cell damage, endovasculitis and fibromyxoid intimal change im arteries and veins, and interstitial pneumonitis with fibrosis.

Polyneuropathy, ophthalmoplegia, leukoencephalopathy, and intestinal pseudo-obstruction: POLIP syndrome.

We describe 5 individuals (from three separate families) with a progressive neurological disorder characterized by sensorimotor peripheral polyneuropathy, cranial neuropathies (external ophthalmoplegia, deafness), and the syndrome of chronic intestinal pseudo-obstruction. Magnetic resonance imaging showed widespread abnormality of the cerebral and cerebellar white matter in the 2 patients studied. Autopsy examination in 3 revealed widespread endoneurial fibrosis and demyelination in the peripheral nervous system, possibly secondary to axonal atrophy, and poorly defined changes in cerebral white matter (leukoencephalopathy). The cranial nerves and spinal roots were less severely involved and the neurons in the brainstem and spinal cord were intact. The fatal gastrointestinal dysmotility was due to a severe visceral neuropathy. We suggest that these patients manifested a hereditary disorder with distinctive clinical, radiological, and neuropathological features, and propose the acronym POLIP to emphasize the distinctive tetrad of polyneuropathy, ophthalmoplegia, leukoencephalopathy, and intestinal pseudo-obstruction.

Arhinencephaly. The spectrum of associated malformations.

Eight cases are presented of arhinencephaly and its associated malformations, which included 2 examples of holoprosencephaly and 3 of agenesis of the corpus callosum. Additional features included cortical malformations, anomalies of the long tracts and of the optic pathway, cerebellar hypoplasia and dentato-olivary dysplasia. Each of these components covered a wide spectrum ranging in severity from extreme to minimal. Craniofacial dysmorphism, and cardiac, renal and endocrine disorders were present in some cases. Only 2 cases were associated with chromosomal abnormalities, 1 with trisomy 13, the other with partial trisomy 7(7q+). Of possible environmental factors, maternal diabetes was recorded in 1 case. While all cases can be classified into broad categories, the individual variations render each case apparently unique.

Necrosis of the fetal brain stem with cerebellar hypoplasia.

Two neonates are presented with intrauterine necrosis of the brain stem. In one of the necrosis and calcification were multifocal and extended from the thalamus to the medulla oblongata. In the other the process was limited to the medulla, but was associated with severe hypoplasia of the nuclei pontis. In both cases the cerebellum was hypoplastic and immature for the gestational age. The connection between the two lesions remains obscure, and two hypotheses are discussed. One hypothesis ascribes the delay in cerebellar development to subliminal damage caused by the same insult that produced the brain-stem lesions, the other considers the possible effects of partial deafferentation on the maturation of the cerebellum.

The amniotic band syndrome as a cause of anencephaly. Report of a case.

The gross and microscopic features of a 28-week-old stillborn female infant with severe cranial, facial, and cerebral malformations due to amniotic bands are described. The structure of the cerebral remnant is similar to that found in dysraphic anencephaly, but collateral evidence of amniotic band can usually be found. It is important to differentiate between the two conditions, since unlike neural tube defects, anencephaly due to amniotic band does not imply a risk of recurrence in subsequent pregnancies.

Intrauterine multisystem atrophy in siblings: a new genetic syndrome?

A condition is described in two siblings, dying in early infancy, characterized by an extreme degree of cerebellar hypoplasia, hypoplasia or atrophy of the brain stem with partial preservation of cranial and spinal nerve nuclei, total degeneration of basal ganglia and thalamus, laminar atrophy of the cerebral cortex, and accumulation of sudanophil lipid in astrocytes and macrophages of the hemispheric white matter. It is suggested that this condition, possibly inherited as an autosomal recessive, may represent a progressive multisystem atrophy occurring in utero, affecting various parts of the neuraxis in different stages in their development.

The neuropathology of glycine encephalopathy: a report of five cases with immunohistochemical and ultrastructural observations.

We studied the spongy myelinopathy of glycine encephalopathy in five patients by using specific antisera. The walls of the vacuoles were stained with the myelin basic protein but not with the myelin associated glycoprotein or the glial fibrillary acidic protein immunostains. The pattern suggested that the vacuoles originated in compact myelin and not from the adaxonal portion of the sheath or from glial processes. Ultrastructural study revealed myelin vacuoles resulting from intraperiod splitting, and there were unusual intranuclear and cytoplasmic inclusions in skeletal muscle in two cases. In addition to the action of glycine as an inhibitory neurotransmitter, structural alterations of myelin may be important in the pathogenesis of the neurologic disorder of glycine encephalopathy.

Amphotericin B-induced myelopathy.

Two patients with coccidioidal meningitis experienced transient neurologic deficits shortly after receiving intrathecal injections of amphotericin B. Continuation of treatment eventually led to a severe flaccid paraparesis with a thoracic sensory level in one patient, and a partial Brown-Séquard's syndrome in the other. Myelography was normal in both, with no evidence of arachnoiditis. Autopsy findings in the first patient showed a focal area of necrosis in the left half of the spinal cord consistent with the patient's clinical findings during life. The distribution of the lesion corresponded to the area supplied by a central sulcal artery. Amphotericin B may exert a direct toxic effect on the spinal cord or its vascular supply when given intrathecally.

Fatal myeloencephalopathy caused by intrathecal vincristine.

Vincristine sulfate was inadvertently given intrathecally to a woman with lymphoma, producing ascending sensory and motor dysfunction followed by encephalopathy and death. Pathologically, neurons were swollen by aggregates of neurofilaments similar to the neurofilaments described in experimental models of vincristine neurotoxicity.

Traumatic lesions of pontomedullary junction.

An autopsied series of 162 consecutive fatal head injuries was analyzed for location and type of primary brain stem injury. Of 41 cases with primary brain stem injury, 24 (59%) demonstrated 22 tears and 2 complete transections at the level of the pontomedullary junction. Three cases are presented in detail to illustrate the range of structural and functional damage seen with trauma at this level of the brain stem. A pathologically verified case of traumatic "locked-in" syndrome is reported, including serial brain stem auditory evoked responses that are correlated with the neuropathological findings. In addition, two cases of primary traumatic damage at the pontomedullary junction (one tear and one total transection) are described; these were associated with instantaneous death at the time of injury. Pathophysiologically, the tearing or disruption occurring at this level results from rapid hyperextension, which produces stretching at the pontomedullary junction.

Fetal exposure to anticonvulsant drugs. Detailed pathological study of a case.

Autopsy findings are discussed of a 23-month-old child exposed in utero to anticonvulsant therapy. Major abnormalities were confined to the heart and brain. The former consisted of massive biventricular hypertrophy with chamber obliteration. Except for generalized cerebral gliosis, the abnormalities in the brain were confined to the cerebellum, where malformation of the dentate nuclei, neuronal heterotopias, and abnormalities of Purkinje's cell dendrites were found. These findings lend further evidence for anticonvulsant teratogenicity.

Oculocerebral malformations. A reappraisal of Walker's 'lissencephaly'.

We describe an infant with multiple ocular and cerebral malformations. The eye lesions included microphthalmia, detachment and dysplasia of the retina, hypoplasia of the optic nerve, persistence of the primary vitreous, cataracts, obliteration of the anterior chamber, and vascularization of the cornea. In the brain, the salient features were microencephaly, agyria of an unusual type, cerebellar hypoplasia and dysplasia, persistent corpus pontobulbare, obliteration of the subarachnoid space, and a midline arachnoid cyst in the posterior fossa. We suggest that these lesions were the end result of a fetal infection that operated during a protracted period starting not later than the fourth month of intrauterine life.

The cytological differentiating potential of pineal parenchymal neoplasms (true pinealomas). A clinicopathological study of 28 tumours.

A series of 28 pineal parenchymal tumours is described, with special reference to the potential of some of these neoplasms to differentiate along glial or ganglionic lines, or both. The more undifferentiated tumours (pineoblastomas, 11 cases) were the most frequent: they are histologically similar to medulloblastomas. One example showed focal differentiation to retinoblastoma at the primary site. The histological features of pineoblastomas merged with those of pineocytomas (7 cases), in which the lobular architecture is reminiscent of that of the mature pineal gland. In addition, 10 further examples in the group of pineocytomas showed more advanced differentiation as follows: towards astrocytes only (2 cases), towards ganglion cells only (1) case) and towards both astrocytes and ganglion cells (gangliogliomas) (7 cases). Confirmation of the pineal parenchymal nature of these neoplasms and of their differentiating potential was provided by a modification of the Achúcarro-Hortega's silver carbonate impregnation technique for pineal parenchymal cells, by specific silver impregnations for axonal processes, and by an immunoperoxidase stain for glial fibrillary acidic (GFA) protein. Electron microscopy of one new example of pineocytoma with neuronal and astrocytic differentiation demonstrated the presence of numerous microtubules, of clear-centred and dense-core vesicles, and of synaptic complexes. Seven illustrative clinical histories with pathological findings are presented. The identification of special features of cellular differentiation is of importance in evaluating the biological behaviour of these neoplasms since a definite correlation can be established between the patient's age, some of the cytological variants, and the malignant potential of the tumour. Pineoblastomas are highly malignant neoplasms of children and young adults which disseminate widely throughout the cerebrospinal fluid pathways. -ineocytomas without cellular evidence of further differentiation occur at any age and are also clinically malignant, but with a somewhat lesser tendency to metastasize than pineoblastomas. Pineobytomas with astrocytic differentiation occur in adults and may be either slowly growing or malignant. Pineocytomas with neuronal or with neuronal and astrocytic differentiation occur in later life, remain localized, and are relatively benign. Since the latter account for approximately one-third of pineal parenchymal tumours and are likely to be relatively radio-resistant, tissue diagnosis is imperative for a determination of the therapeutic approach. Radiation to the entire neuraxis should be administered to patients with pineoblastomas and malignant pineocytomas in view of their high frequency of cerebrospinal metastasis. An accurate histological classification of these tumours therefore carries important clinical and therapeutic implications...

Displacement of cerebellar tissue into spinal canal. A component of the respirator brain syndrome.

Displacement of cerebellulr tonsillar tissue into the subdural and subarachnoid space around the spinal cord was found at autopsy in eight patients who had had a variety of neurological diseases. The common factors were brain swelling and prolongation of survival by the respirator from 14 to 96 hours. Superimposed massive edema and intravitam autolysis caused by the artificial prolongation of life was the final outcome and is the most important factor in the pathogenesis of this condition. Unless the spinal cord has been examined, many pathological changes will not be appreciated.