A Pacchionian Puzzle.

A 73-year-old male with a history of chronic ataxia presented with transient facial droop to the Emergency Department. A CT angiogram and MRI with diffusion weighted imaging (DWI) were negative for stroke. However, incidental note was made of numerous giant arachnoid granulation pits in the posterior fossa predominantly involving the left occipital bone (Figure 1). These arachnoid pits demonstrated multiple foci of herniation of the adjacent cerebellar parenchyma into the pits with gliosis of the herniated parenchyma and focal encephalomalacia of the subjacent cerebellar parenchyma. Review of bone windows on a remote CT brain performed almost 13 years earlier confirmed this to be a longstanding abnormality (Figure 2). The patient's physical exam was suggestive of cerebellar ataxia with left-sided dysmetria on finger to nose testing and a wide-based unsteady gait.

Surgical outcomes and prognostic factors of drug-resistant epilepsy secondary to encephalomalacia.

OBJECTIVE: To evaluate long-term outcomes and prognostic factors in patients who underwent surgical resection for drug-resistant epilepsy secondary to encephalomalacia. METHODS: A total of 143 patients with drug-resistant epilepsy who underwent surgical resection with a follow-up of at least 5 years were included. Seizure outcomes were evaluated based on the International League Against Epilepsy classification. Univariate analysis and a multivariate logistic regression model in a backward fashion were used to identify the potential predictors of seizure outcomes. RESULTS: Three months after surgery, 102 of 143 (71.3%) patients had achieved favorable seizure outcomes. Five years after surgery, 107 of 143 (74.8%) patients had achieved favorable seizure outcomes. Changes in the postoperative seizure status were observed in 22 of 143 (15.4%) patients during follow-up, but the difference in the seizure-free rate between 3 months and 5 years after surgery was not significant. Univariate and multivariate analyses revealed that only a monthly seizure frequency of >30 seizures (odds ratio = 3.42, 95% confidence interval = 1.19-9.76) and bilateral ictal onset rhythms (odds ratio = 4.46, 95% confidence interval = 1.61-12.39) were independent predictors of unfavorable seizure outcomes. SIGNIFICANCE: Surgical resection is an effective treatment for patients with drug-resistant epilepsy secondary to encephalomalacia. Knowledge of the predictors of seizure outcomes may help during preoperative counseling and selection of optimal candidates for epilepsy surgery among patients with drug-resistant epilepsy secondary to encephalomalacia.

The ketogenic diet for medically and surgically refractory status epilepticus in the neurocritical care unit.

BACKGROUND: Refractory status epilepticus carries a high risk of morbidity and mortality despite, and at times as a result of, aggressive pharmacologic interventions. Dietary therapies have been used for almost a century in children for controlling medically refractory seizures and status epilepticus and recent studies suggest efficacy and safety in adults as well. METHODS: Case report and literature review. RESULTS: We describe a case of medically and surgically refractory status epilepticus that was controlled after initiation of the ketogenic diet and maintenance with the modified Atkins diet in an adult in the neurocritical care unit. CONCLUSIONS: Dietary therapy should be considered as a treatment option in adult patients with refractory status epilepticus.

Cerebromalacia with epilepsy and cortical blindness in a laboratory Japanese macaque (Macaca fuscata).

The authors performed a pathological examination of a 5-year-old female laboratory Japanese monkey who developed cortical blindness and epileptic seizures. Generalized, tonic-clonic seizures started to occur during behavioral training to get the animal to enter a carrying cage for future psychological experiments. Blindness was suspected because of a lack of approaching behavior toward foods such as fruits. Although the monkey was extensively treated with anticonvulsants, the clinical signs did not improve. An increased serum creatine phosphokinase (CPK) level and bilateral occipital brain atrophy were detected. Histopathologically, a severe degree of cerebromalacia was detected bilaterally in the occipital lobe, and necrosis and gliosis were seen mainly in the temporal lobe. Focal inflammation was found in the meninges. No other changes were observed in other nervous tissues or organs, and no signs of a parasitic or viral infection were found in the systemic organs. Spontaneously occurring lesions in the central nervous system have been rarely reported in laboratory monkeys. In the present case, the cause of cerebromalacia could not be confirmed, but the relationship between symptoms such as abnormal vision and the presence of brain lesions was distinct. The authors believe that this case is a valuable historical control case for the laboratory Japanese macaque.

The impact of MEG results on surgical outcomes in patients with drug-resistant epilepsy associated with focal encephalomalacia: a single-center experience.

PURPOSE: To analyze the impact of magnetoencephalography (MEG) results on surgical outcomes in patients with drug-resistant epilepsy secondary to encephalomalacia. METHODS: We retrospectively reviewed 121 patients with drug-resistant epilepsy associated with encephalomalacia who underwent MEG followed by resection surgery. Patients were subdivided into concordant MEG group and dis-concordant MEG group for analysis based on whether the MEG results were in concordance with epileptogenic zones or not. RESULTS: 121 patients were included in the present study. The MEG spike sources of 73 (60.33%) patients were in concordance with epileptogenic zones while the MEG spike sources of the other 48 (39.67%) were in dis-concordance with epileptogenic zones. Favorable seizure outcomes were achieved in 79.45% (58 of 73) of patients with concordant MEG results while only 62.50% (30 of 48) of patients with dis-concordant MEG results were seizure free with a follow-up of 2-10 years. The differences of seizure-free rate between patients with concordant MEG results and dis-concordant MEG results were statistically significant. For patients with concordant MEG results, bilateral lesions on MRI are the only independent predictor of unfavorable seizure outcomes. For patients with discordant MEG results, duration of seizures is the only independent predictor of unfavorable seizure outcomes. CONCLUSIONS: Concordant MEG results are associated with favorable seizure outcomes. Bilateral lesions on MRI independently predict unfavorable seizure outcomes in patients with concordant MEG results while longer seizure durations independently predict unfavorable seizure outcomes in patients with dis-concordant MEG results.

Route learning impairment associated with encephalomalasia secondary to traumatic brain injury: a case report.

Topographical disorientation is marked by difficulty finding one's way in familiar or new environments. The present case study reports findings from a 30-year-old male with encephalomalasia of the left parahippocampal region secondary to brain trauma with subsequent difficulty in learning of new routes. His navigation in premorbidly known (familiar) surroundings was intact. Magnetic resonance images revealed left parahippocampal and bilateral occipital encephalomalasia. Neuropsychological screening showed impairment in structuring a representation of the spatial relationships among landmarks with relatively preserved ability to learn visual and verbal information of these landmarks. Decreased visual perception and inappropriate visual inputs due to cervical dystonia and right homonymous hemianopsia also appear to play a role in his disability. The current knowledge about the neuronal systems involved in visual cognition and topographical orientation also are addressed in this report.

Early destructive lesions in the developing brain: clinical and electrographic correlates.

OBJECTIVE: Early brain insults can cause cavitary lesions including porencephaly (POR) and multicystic encephalopathy (MCE). The objective of this study was to investigate clinical and electrographic correlates associated to these types of destructive brain lesions. METHOD: Patients with POR and MCE were selected and submitted to clinical and Video-EEG monitoring. The following variables were analyzed: demographic data, type of lesion, presence of gliosis, perinatal complications, epilepsy, brain atrophy, and presence and frequency of epileptiform discharges. RESULTS: Twenty patients were included, 65% males, 35% females, ages ranging from 1 to 40 years, 14 with MCE and 6 with POR. Eighteen patients had hemiparesis, 19 had epilepsy (current or in the past), seven of them had refractory seizures, and 16 had epileptiform discharges. All patients with MCE had gliosis while only 2 with POR had it. CONCLUSIONS: No correlation was observed between type of lesion and clinical and electrographical outcome. However, a positive correlation was observed between frequency of discharges and presence of brain atrophy, and between MCE and gliosis.

Abnormal parietal encephalomalacia associated with schizophrenia: A case report.

RATIONALE: It is widely believed that structural abnormalities of the brain contribute to the pathophysiology of schizophrenia. The parietal lobe is a central hub of multisensory integration, and abnormities in this region might account for the clinical features of schizophrenia. However, few cases of parietal encephalomalacia associated with schizophrenia have been described. PATIENT CONCERNS AND DIAGNOSES: In this paper, we present a case of a 25-year-old schizophrenia patient with abnormal parietal encephalomalacia. The patient had poor nutrition and frequently had upper respiratory infections during childhood and adolescence. She showed severe schizophrenic symptoms such as visual hallucinations for 2 years. After examining all her possible medical conditions, we found that the patient had a lesion consistent with the diagnosis of encephalomalacia in her right parietal lobe and slight brain atrophy. INTERVENTIONS: The patient was prescribed olanzapine (10 mg per day). OUTCOMES: Her symptoms significantly improved after antipsychotic treatment and were still well controlled 1 year later. LESSONS: This case suggested that parietal encephalomalacia, which might be caused by inflammatory and infectious conditions in early life and be aggravated by undernutrition, might be implicated in the etiology of schizophrenia.

MEG May Reveal Hidden Population of Spikes in Epilepsy With Porencephalic Cyst/Encephalomalacia.

Porencephalic cyst/encephalomalacia is often associated with intractable epilepsy. A limited number of studies reported magnetoencephalography's (MEG's) potential to help construct treatment strategy for epilepsies associated with porencephalic cyst/encephalomalacia. The authors present here simultaneous electroencephalography (EEG) and MEG findings in three adult patients with pediatric-onset epilepsy due to porencephalic cyst/encephalomalacia. There were two types of spikes: one type was detected by MEG only (EEG-/MEG+), and the other detected by both EEG and MEG (EEG+/MEG+). Both types were seen in all three cases. The EEG-/MEG+ spikes all formed tight clusters; in contrast, the majority of EEG+/MEG+ spikes formed loose clusters. These data suggest that MEG may be helpful to better identify spike populations in epilepsy patients with porencephalic cyst/encephalomalacia. If hidden spike populations were to be found by MEG, this information would affect the interpretation of patient's pathophysiology and planning of intracranial electrode placement.

Hyperprolactinemia presenting with encephalomalacia-associated seizure disorder and infertility: a novel application for bromocriptine therapy in reproductive endocrinology.

OBJECTIVES: To describe successful oral bromocriptine therapy for hyperprolactinemia accompanied by seizure disorder and encephalomalacia identified during infertility evaluation. MATERIALS & METHODS: A 32 year-old male with an unspecified seizure disorder was referred for infertility consultation. The initial seizure was at age 12, and was treated sequentially with phenytoin, phenobarbitol, and carbamazepine monotherapy which was maintained for six years and then discontinued. At age 26, a second seizure was experienced and 150mg lamotrigine b.i.d. was initiated. When the patient married it was discovered that erection was impossible; tadalafil was administered without success. At our center, total testosterone was low at 107ng/dl and semen analysis revealed oligoasthenozoospermia. Serum prolactin was 79.3ng/ml; visual field examination was normal. Brain MR showed no pituitary enlargement. However, encephalomalacia of the right occiptal lobe with porencephalic dilation of the occipital horn of the right lateral ventricle was present. RESULTS: The patient was initially placed on 2.5mg/d bromocriptine but after three months only a nominal reduction of serum prolactin was achieved. Serum prolactin normalized (25.4ng/ml) after bromocriptine was increased to 7.5mg/d. Repeat semen analysis showed overall sperm concentration of 85M/ml, 30% motility and 12% normal forms morphology (Kruger strict criteria). Total testosterone level was 191ng/dl after final bromocriptine dose was attained, which was well tolerated. DISCUSSION: Bromocriptine has an established role in the management of hyperprolactinemia, particularly in women. For males with elevated serum prolactin even when associated with focal encephalomalacia and seizure disorder, bromocriptine therapy can offer safe benefits including improved semen parameters and normal serum testosterone levels.

Multicystic encephalomalacia: An autopsy report of 4 cases

Multicystic encephalomalacia is varying sized cystic lesions in the brain encountered in developing fetuses or infants. These cysts start at the periventricular area and may extend onto the cortex. The cause of the formation of these cystic lesions is secondary to an ischemic or hypoxic insult, which leads to liquefactive necrosis and subsequent formation of gliotic cyst walls having an admixture of microglia. We discuss four autopsy cases that had multicystic encephalomalacia to highlight the scenarios in which these lesions are encountered.

Cerebrospinal fluid oligoclonal IgG bands in patients with spinal arteriovenous malformation and structural central nervous system lesions.

OBJECTIVE: To investigate the incidence and characteristics of patients with structural central nervous system (CNS) lesions and cerebrospinal fluid oligoclonal IgG bands. DESIGN: A retrospective study. METHOD: The medical records of patients with cerebrospinal fluid oligoclonal IgG bands were evaluated for the presence of structural CNS lesions, their location and cause, and for clinical characteristics. SETTING: Cerebrospinal fluid oligoclonal IgG bands were examined in the Neuroimmunology Laboratory, Hadassah University Hospital, Jerusalem, Israel. PATIENTS: Two hundred seventy of 570 patients with positive cerebrospinal fluid oligoclonal IgG bands were available for analysis. Twenty patients had structural CNS lesions. RESULTS: Twenty (7.5%) of the 270 patients had structural CNS lesions: 3 patients had spinal arteriovenous malformation; 5 patients had tumors; 9 patients had compressive cervical myelopathy. Traumatic leukomalacia, Arnold-Chiari malformation type 1, and CNS hemosiderosis were present in 1 patient each. In 2 patients (1 patient with recurrent meningioma and 1 patient with posttraumatic encephalomalacia) the presence of a structural CNS lesion was followed by the development of multiple sclerosis. In all 3 patients with spinal arteriovenous malformation, oligoclonal IgG identification prolonged the time to diagnosis and therapy, which varied from a few weeks to 3 years. CONCLUSIONS: Structural CNS lesions, responsible for the neurological disorder, were present in 20 patients (7.5%) with cerebrospinal fluid oligoclonal IgG bands. The mechanism underlying oligoclonal IgG presence in spinal arteriovenous malformation and the coexistence of multiple sclerosis and structural CNS lesions is unknown, but may be related to recurrent tissue damage with repeated presentation of CNS antigens to the immune system.

Complex acid-base disorders in subacute necrotizing encephalomyelopathy (Leigh's syndrome).

This report describes a case of subacute necrotizing encephalomyelopathy (Leigh's syndrome) in a 7-month-old boy. The clinical data suggest an association with a disorder of renal tubular acidification, characterized by both (proximal) type II and (distal) type I renal tubular acidosis (hybrid type). Concomitantly, the initial uncompensated metabolic acidosis evolved into a mixed metabolic acidosis and respiratory alkalosis-features of this syndrome not previously reported.

Bilateral symmetrical softening of the thalamus.

The clinical and pathological data of a 48 year old patient who survived 40 days are reported. Her disturbance of consciousness corresponded to an apallic syndrome, which 12 days later bacame akinetic mutism. Symmetrical softening involving the medial thalamic nuclei from the plane of the corpora mamillaria to the red nuclei was found. The ischemic lesion might be explained by transient circulatory collapse combined with hypoplasia of the vertebrobasialr arteries. On the EEG slight irregular alpha activity was recorded (alpha coma) and external stimuli elicited theta-delta waves (paradox activation). A survey of the literature of akinetic mutism is included and the correlation between non-hypnoid unconsciousness and EEG is discussed.

Obstructive hydrocephalus caused by intraventricular collapse of malacotic brain. Case report.

The authors present the case of a 68-year-old man who experienced acute obstructive hydrocephalus after having suffered an infarction in the occipital lobe. Histopathological and serial neuroimaging examinations revealed that portions of a large disintegrating occipital infarct had entered the lateral ventricle and obstructed the passage of cerebrospinal fluid (CSF). Ventricular drainage was performed for 2 weeks until the patient's hydrocephalus resolved. The CSF initially contained a high concentration of protein (1070 mg/dl), a high leukocyte count of 115 cells/mm3, and a rich fibrinous exudate. Findings in the present case indicate that collapse of a periventricular ischemic lesion into the ventricles may sometimes occur not only after cerebral hemorrhage but also after cerebral infarction.

Relationship between periventricular hemorrhage, leukomalacia and brainstem lesions in prematurely born infants.

The brain pathology in very prematurely born infants with intraventricular hemorrhage (IVH) was studied particularly as to the severity and site of the complicated brain lesions responsible for the prognosis. A high frequency of leukomalacia, pontosubicular necrosis and/or olivocerebellar neuronal loss was found in the cases of IVH, and these non-hemorrhagic brain lesions showed an increasing frequency with the grade of IVH. However, there was marked reduction of IVH, periventricular leukomalacia and, in particular, brainstem lesions in prematurely born cases of sudden infant death. These IVH and associated conditions have different pathogenesis, but factors responsible for their occurrence may be present together in each case.

MRI in motor delay: important adjunct to classification of cerebral palsy.

Cranial magnetic resonance imaging (MRI) was performed prospectively in 45 children (ages 3-27 months) with clinically documented motor delay to evaluate the ability of MRI to determine etiologic factors, to determine whether myelination correlated with motor delay, and whether the clinical category corresponded with the imaging findings. Of the 22 children diagnosed clinically as having major motor delay (i.e., cerebral palsy), 77% had magnetic resonance imaging abnormalities. In 23%, etiologic associations were established from MRI alone and in 32% a clinically suspected etiology was supported. No children had myelination delay as the sole abnormality. In 23 children with minor motor delay, only 17% had abnormal scans. Clearly, MRI provided useful information in the majority of children with cerebral palsy; therefore, a classification system is proposed in which MRI can be used in conjunction with clinical assessment to specify more precisely the etiologic factors in cerebral palsy.

Neurodevelopmental outcome of periventricular haemorrhage and leukomalacia in infants 1250 g or less at birth.

The brains of 50 consecutively admitted infants weighing 1250 g or less at birth were serially examined beyond the neonatal period for periventricular haemorrhage and for periventricular leukomalacia with real-time ultrasound. There was significant correlation between the presence or absence and the severity of haemorrhage with survival. A prospective neurodevelopmental assessment was completed at 2 years of age, corrected for prematurity, on all survivors. None of the 20 survivors with normal scans or germinal layer haemorrhages had evidence of major disability and all four survivors with intracerebral haemorrhage or periventricular leukomalacia had major disability. The mental performance on the Bayley scales of infant development was also significantly worse in the latter group. Six of the eight survivors with intraventricular haemorrhage had no major disability, including three who had post-haemorrhagic hydrocephalus. Our results showed that cerebral ultrasound detection of brain pathology is a good predictor of neurodevelopmental outcome in such extremely low birthweight infants. However, as the maximum extent of periventricular haemorrhage may develop beyond one week of age and cystic periventricular leukomalacia commonly develops after the neonatal period, serial scanning is mandatory to ensure diagnostic accuracy for both periventricular haemorrhage and leukomalacia.

Multicystic encephalomalacia associated with symmetrical necrotizing brain stem lesions in an infant: a case report.

The simultaneous occurrence of multicystic encephalomalacia of the cerebral hemispheres, and symmetric necrotizing lesions of diencephalic and infratentorial structures is described in a 15 month-old infant. The baby developed clonic jerks of four limbs a few hours after delivery. She attained no developmental milestones, and remained bed-ridden with hypertonic posture until her death. Multicystic cavities of the cerebral hemispheres were well evident at CT scan when she was 7 months old. The topographic distributions of the different pathological pictures are described; their relationship to the regional properties of the developing brain are commented upon. Etiological aspects of this case are discussed according to present knowledge of the pathophysiological mechanisms leading either to multiple cyst formation or to necrotizing lesions.