Alzheimer's disease: a review concerning immune response and microischemia.

Alzheimer's disease (AD), as we think of it today, is the idiopathic progressive loss of cognitive function over a period of several years. The risk of late onset dementia increases significantly with each decade of life such that half of the population over the age of 80 is vulnerable to this disease (1). We know that proper functioning of the central nervous system is dependent on adequate blood flow to remove harmful metabolic products and supply nutrients such as glucose and oxygen to the brain. It has been suggested that cerebral hypoperfusion causes AD (2). Mean cerebral blood flow decreases with age and with sclerosis of cerebral blood vessels. Blood flow appears to increase in stimulated areas of the brain during different activities. However, there is a derangement of blood flow in disease states; this has been documented in the temporal lobes of AD patients, (3,4). English language journal articles located by a MEDLINE search (1960-1999) were reviewed with consideration to the hypothesis that Alzheimer's disease is an autoimmune disease initiated by low oxygen tension and microischemia. Inflammation is thought to be a known contributor to the pathology of AD (5,6). Recent reports support the concept of autoimmunity as a final common pathway of neuron death, particularly for cholinergic in Alzheimer's disease (6). A model of Alzheimer's disease is proposed and related research and treatment modalities are discussed.

Fatal infantile X-linked neuropathy.

We report a pedigree with severe X-linked neuropathy that occurs in male infants and results in death, typically by 2 years of age. The proband of our report was weak with preserved mentation. He underwent extensive evaluation, which revealed abnormal nerve conduction studies, neurogenic changes on muscle biopsy, a decreased number of large myelinated fibers and rare onion bulb formations on nerve biopsy, negative gene testing for spinal muscular atrophy, CMT1a, and CMTX1 and a normal brain magnetic resonance image. The proband's mother, an obligate carrier, had normal nerve conduction studies. Male infants with a spinal muscular atrophy phenotype but normal genetic studies should be evaluated for this fatal X-linked neuropathy.

The significance of ictal depth EEG patterns in patients with temporal lobe epilepsy.

We reviewed 187 depth recorded seizures in 33 patients with non-lesional temporal lobe complex partial seizures. All patients had a minimum of 1 year follow-up following temporal lobectomy. We classified seizure onset pattern as rhythmic activity, attenuation, or repetitive spikes or spike wave complexes. The most common pattern of seizure onset was rhythmic activity and the next most common pattern was repetitive spikes. Seventy-five seizures (49%) had only one seizure onset pattern, and 79 seizures (51%) had a combination of seizure onset patterns. The degree of hippocampal gliosis strongly predicted the type of seizure onset pattern (Chi square = 24.07, 2 d.f., P < 0.01). The rhythmic activity pattern was associated with mild gliosis, and the repetitive spike pattern was associated with severe gliosis. We classified seizure onset as focal or regional based on the number of electrode contacts that were involved by the ictal EEG. A focal seizure onset was associated with an excellent outcome following temporal lobectomy.

Dementia associated with dorsal midbrain lesion.

Although the dorsal midbrain has been implicated in cognitive processes in animals, its role in humans is unclear. We report the neuropsychological and postmortem neuropathological findings of a 52-yr-old university professor who developed a profound dementia in association with a focal dorsal midbrain lesion. The patient's disorder appeared to result from a tuberculous granuloma based on the clinical course and autopsy results. Neuropsychologically, he exhibited a generalized impairment across most of the cognitive domains assessed. His deficits were not explained by impaired arousal, specific sensory or motor defects, depression, or hydrocephalus. Although there are inherent limitations to a single-case investigation, our observations are consistent with animal studies that have demonstrated that focal dorsal midbrain lesions may result in cognitive impairment. We propose that the dorsal midbrain is involved in cognitive processing via modulation of thalamocortical networks.

Seizure localization in temporal lobe epilepsy: a comparison of scalp-sphenoidal EEG and volumetric MRI.

We determined the accuracy of volumetric MRI (based on identification of unilateral hippocampal atrophy) and scalp-sphenoidal EEG (based on concordant interpretations of scalp-sphenoidal ictal EEG by three independent interpreters) for seizure focus localization in 20 patients with temporal lobe epilepsy. All patients became seizure-free or had rare seizures following temporal lobectomy. Among the 20 patients, nine (45%) met both MRI and EEG localization criteria, six (30%) met MRI localization criteria alone, three (15%) met EEG localization criteria alone, and two patients (10%) did not meet either localization criteria. In the 18 patients meeting MRI or EEG localization criteria, the predicted localization agreed with the side of temporal lobectomy. These results suggest that a noninvasive approach combining MRI and EEG will correctly localize the side of seizure onset in most patients with temporal lobe epilepsy.

Magnetic resonance imaging in childhood intractable partial epilepsies: pathologic correlations.

We conducted a retrospective single-blind study assessing the value of MRI in 44 children surgically treated for partial epilepsy, and correlated the MRI findings with the pathology in all cases. MRI revealed abnormalities in concordance with the clinical and electroencephalographic data in 84% of patients. Developmental neuronal migration pathology was present in 25% of patients and was relatively more common in the sensorimotor cortex. There was hippocampal sclerosis in 50% of patients with temporal lobe resection; however, only two of the 10 children with hippocampal sclerosis were below the age of 12 years. Similarly, ganglio-glial tumors were more common than astrocytomas in children below age 12. These results indicate that MRI is sensitive in the detection of pathologic abnormalities in most pediatric candidates for epilepsy surgery, and that the distribution and type of pathology appear to be age related in this population.

Comparative neuroimaging with pathologic correlates in Alexander's disease.

We describe a case of pathologically confirmed Alexander's disease in which serial cranial ultrasound studies demonstrated unique findings of enlarging subependymal cysts with evolving periventricular hyperechogenicity. Computed tomographic scan of the head showed low attenuation of the periventricular white matter and centrum semiovale. Magnetic resonance imaging (MRI) demonstrated diffuse, confluent high signal predominantly in frontal white matter. These imaging modalities, particularly cranial ultrasound and MRI, may be useful tools in the diagnostic evaluation of children with degenerative neurologic disease, megalencephaly, and suspected Alexander's disease.

MR imaging in patients with intractable complex partial epileptic seizures.

Detailed neurologic studies, high-field-strength MR imaging, and CT scanning were performed preoperatively in 53 patients with intractable complex partial seizures who underwent surgical treatment for epilepsy. Macroscopic structural (tumoral or vascular) lesions were found in 28% of patients. The remainder had pathologic findings consistent with mesial temporal gliosis. Tumors were found in 22% of the patients and were benign or of low-grade malignancy in every case. MR was accurate in the preoperative diagnosis of structural lesions, including very small occult tumors and cryptic vascular malformations. In patients with mesial temporal gliosis, there was correlation between the MR observation of a unilaterally dilated anterior temporal horn and the EEG-identified seizure focus and side of temporal lobectomy. However, MR demonstrated T2-weighted signal abnormalities correlating with the epileptogenic focus in only 8% of cases of mesial temporal gliosis. MR provided useful information in 28% of patients who underwent surgery for refractory complex partial epilepsy. MR obviated invasive EEG monitoring in 93% of the patients with structural lesions. MR was useful in only 8% of the patients with pathologic changes of mesial temporal gliosis.

MR imaging in patients with intractable complex partial epileptic seizures.

Detailed neurologic studies, high-field-strength MR imaging, and CT scanning were performed preoperatively in 53 patients with intractable complex partial seizures who underwent surgical treatment for epilepsy. Macroscopic structural (tumoral or vascular) lesions were found in 28% of patients. The remainder had pathologic findings consistent with mesial temporal gliosis. Tumors were found in 22% of the patients and were benign or of low-grade malignancy in every case. MR was accurate in the preoperative diagnosis of structural lesions, including very small occult tumors and cryptic vascular malformations. In patients with mesial temporal gliosis, there was correlation between the MR observation of a unilaterally dilated anterior temporal horn and the EEG-identified seizure focus and side of temporal lobectomy. However, MR demonstrated T2-weighted signal abnormalities correlating with the epileptogenic focus in only 8% of cases of mesial temporal gliosis. MR provided useful information in 28% of patients who underwent surgery for refractory complex partial epilepsy. MR obviated invasive EEG monitoring in 93% of the patients with structural lesions. MR was useful in only 8% of the patients with pathologic changes of mesial temporal gliosis.

Neuropathological abnormalities in developmental dysphasia.

The brain of a 7-year-old girl with developmental dysphasia who died of complications of infectious mononucleosis was examined grossly and histologically. The neuropathological studies revealed atypical symmetry of the plana temporale and a dysplastic gyrus on the inferior surface of the left frontal cortex along the inferior surface of the sylvian fissure. These anomalies are likely related to midgestation, the period of neuronal migration from the germinal matrix to the cerebral cortex, and are consistent with a neurodevelopmental cause of developmental dysphasia.

Central pontine myelinolysis and pregnancy.

Central pontine myelinolysis, also known as osmotic demyelination syndrome, is an uncommon disorder associated with rapid correction of severe hyponatremia. We present the case of a healthy young pregnant woman with hyperemesis gravidarum who developed severe hyponatremia (serum sodium 103 mEq/L). After rapid correction of her serum sodium within 12-15 hours with a 0.9% saline solution, the patient became comatose and died of sepsis and respiratory failure. Examination of the brain showed extensive demyelination in both pontine and extrapontine areas.

Generalized chorea due to basal ganglia lacunar infarcts.

Although hemichorea is often ascribed to a vascular lesion, generalized chorea of adult onset is often thought to be due to degenerative diseases. We describe a 74-year-old woman with generalized chorea that was diagnosed at autopsy as due to multiple lacunar infarcts in the basal ganglia. Generalized chorea in adults may be caused by vascular disease of the basal ganglia.

Severe central nervous system toxicity from high-dose cytarabine: expressive aphasia occurring after the second day of treatment.

A patient with acute erythroleukemia secondary to polycythemia vera was treated iv with high-dose cytarabine at a dose of 3 g/m2 every 12 hours. After the fourth dose, he developed an expressive (Broca's type) aphasia and somnolence, which progressed until after the treatment was stopped at the seventh dose. The somnolence cleared partially during the next 2 weeks but recurred after cytarabine was restarted at a dose of 100 mg/m2 daily for 7 days. The patient died 5 days later of refractory extreme thrombocytopenia and bleeding. The normal spinal fluid obtained during life and the postmortem findings were consistent with previously reported findings with central nervous system toxicity from high-dose cytarabine. Three unusual aspects of this case are early onset of symptoms, expressive aphasia as the dominant manifestation, and exacerbation of symptoms with standard doses (100 mg/m2/day).

An immunochemical investigation of 2':3'-cyclic nucleotide 3'-phosphodiesterase (CNP) in bovine cerebrum and human oligodendroglioma.

Bovine cerebrum, including the corpus callosum, and a human oligodendroglioma were investigated by an immunohistochemical technique to determine the distribution of 2':3'-cyclic nucleotide 3'-phosphodiesterase (CNP). Also, three human oligodendrogliomas (ODG) were characterized by an immunoblot procedure to identify a protein(s) with cross-reacting determinants to CNP and assayed for CNP activity. CNP was localized to oligodendrocytes in the corpus callosum and subcortical white matter and gray matter. Also, nerve fibers appeared to be stained. Further, cells of the human oligodendroglioma were immunostained which were similar in morphology to those cells stained in the bovine cerebrum; however, fewer than 5% of the oligodendroglioma cells were immunostained. Immunoblotting revealed two separate and distinct bands for the three oligodendrogliomas, showing cross-reactivity to bovine CNP antisera at about 53,000 and 46,000 daltons. Specific CNP activity of the three human oligodendrogliomas ranged from 0.4 to 1.6 mumole of 2':3'-cAMP hydrolyzed/min/mg protein.

Herpes simplex virus recovery in neural tissues after ocular HSV shedding induced by epinephrine iontophoresis to the rabbit cornea.

Ocular HSV-1 shedding from latently infected rabbits was induced by iontophoresis of 0.01% epinephrine into the eye. Anodal Iontophoresis of epinephrine was performed at 0.8 mAmps for 8 min once a day for 3 consecutive days. Shedding was determined by the presence of HSV-1 in the preocular tear film obtained via eye swabs. Bilateral epinephrine iontophoresis performed on selected days during 220-280 days after inoculation resulted in HSV-1 shedding in 75% of the eyes (30/40) and 100% of the rabbits (20/20). Following the induction of ocular HSV-1 shedding, rabbits were killed and selected neural tissues were homogenized. Cell-free preparations were assayed for the presence of infectious virions using primary rabbit kidney cell monolayers. When the tissues were homogenized immediately after death, virus was detected in only one neural tissue, the trigeminal ganglia. However, when the tissues were incubated in vitro for 18-24 hours prior to the homogenization, infectious HSV-1 was recovered from homogenates of the trigeminal ganglion, superior cervical ganglion, the ophthalmic branch of the trigeminal nerve, and the root entry zone of the trigeminal nerve. A relationship was noted between the time of the last ocular shedding and recovery of infectious HSV from the tissue homogenates. Furthermore, a positive correlation in 11 eyes between the recovery of HSV-1 from the perocular tear film and HSV-1 recovery from one or more corresponding neural tissues was found. These results suggested that epinephrine iontophoresis to the cornea triggered an "alteration" in the state of the virus in the neural tissues of the latently infected rabbits and that the change can be related to the induced ocular shedding.

Near-drowning complicated by brain abscess due to Petriellidium boydii.

Extracutaneous infection from Petriellidium boydii is an unusual occurrence despite the ubiquity of the organism in nature. Central nervous system infection by this organism is extremely rare, only seven previous reports having been found. The rarity of this manifestation prompted the report of a brain abscess occurring in a previously healthy youth after a near-drowning. The source of the infection was likely to have been the river water at the accident site, from which P boydii was isolated. Although previous in vitro susceptibility data and failure of amphotericin B therapy in a similar infection suggested miconazole treatment might be beneficial, the organism causing the brain abscess was resistant to miconazole and amphotericin B. This report emphasizes the urgent need for safer and more predictably effective alternatives to currently available antifungal agents.

Cervical myelopathy due to spondylosis. Case report.

The authors report the case of a patient with cervical myelopathy who was examined at autopsy 2 years after a second anterior cervical fusion by Cloward's technique. The clinical course and pre- and postoperative myelograms are presented. Theories as to the etiology of myelopathy are discussed. This case demonstrates chronic changes that seem to implicate a vascular theory but not the specific vessel or vessels. The mechanism of improvement following the Cloward procedure is not explained by the pathological slides.