The axonal damage marker tau protein in the cerebrospinal fluid is increased in patients with acute encephalopathy with biphasic seizures and late reduced diffusion

Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is a recently clinicoradiologically-established encephalopathy syndrome. In the present study, we examined the levels of cerebrospinal fluid (CSF) tau protein, a marker of axonal damage, in 11 patients with AESD. CSF tau levels were normal on day 1 and increased from day 3 of the disease between the initial and the secondary seizures. Magnetic resonance imaging (MRI) reveals reduced diffusion in the subcortical white matter during days 3–7. Two patients showed elevated tau protein prior to the diffusion abnormality of subcortical white matter on MRI. Levels of CSF neuron specific enolase (NSE), a neuronal marker, were elevated in only two out of seven patients with AESD, and CSF tau levels were also increased in these patients. Our results indicated that tau protein is a more sensitive marker than NSE and axonal damage causes the conspicuous MRI findings in AESD patients. A therapeutic strategy for axonal protection should be developed to prevent severe neurological impairment of AESD patients.     

Two newly proposed infectious encephalitis/encephalopathy syndromes

Two newly proposed infectious encephalitis/encephalopathy syndromes, in which magnetic resonance imaging (MRI) is essential for the diagnosis, have been reviewed. Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is reported only in East Asian infants, characterized by a febrile seizure (usually >30 min) as the initial neurological symptom on day 1, followed by secondary seizures at day 4 to 6; affected children display variable levels of neurological sequelae. MRI shows no acute abnormality during the first two days; reduced diffusion appears in the frontal or fronto-parietal subcortical white matter during days 3 to 9, then disappears between days 9 and 25. Excitotoxic injury with delayed neuronal death is hypothesized as a possible mechanism based on MR spectroscopic findings.     

A case of acute encephalopathy with biphasic seizures and late reduced diffusion associated with Streptococcus pneumoniae meningoencephalitis

Acute encephalopathy with biphasic seizures and reduced diffusion (AESD) encompasses a group of encephalopathy characterized by biphasic seizures and disturbance of consciousness in the acute stage followed in the subacute stage by reduced diffusion in the subcortical white matter on magnetic resonance imaging. The etiology of AESD is viral infection and associated pathological changes. Here we report the first case of AESD caused by bacterial infection (Streptococcus pneumoniae meningitis) in a 1-year-old boy.     

Acute encephalopathy with biphasic seizures and late restricted diffusion on MRI in a Japanese child living in the USA

We report an 18-month-old Japanese female living in the USA whose clinical course and radiographic findings were consistent with acute encephalopathy with biphasic seizures and late reduced diffusion (AESD). She was initially diagnosed with complex febrile seizures. However, on day 3 of admission, she had a cluster of complex partial seizures and the onset of a global developmental regression. In contrast to the normal magnetic resonance image of the brain obtained on admission, subsequent imaging demonstrated transient subcortical diffusion-weighted abnormalities in the white matter of the bilateral posterosuperior frontal, parietal, temporal, and occipital regions, with sparing of the perirolandic area. One year later, her developmental delay, although improved, persisted and she continued to experience sporadic seizures while being treated with topiramate monotherapy. Repeat imaging showed diffuse, poorly defined, increased T2 signals in the white matter of the posterosuperior frontal, parietal, temporal and occipital regions and diffuse cerebral volume loss. Previous reports of AESD have been limited to children aged under 4 years living in Japan. With the identification of this case, it is important that all physicians, not only those in Japan, who care for children with febrile seizures be aware of AESD and its associated neurological morbidity.     

Two cases of traumatic head injury mimicking acute encephalopathy with biphasic seizures and late reduced diffusion

Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) presents a distinct clinical course of biphasic seizures and impaired consciousness. These symptoms are followed by reduced diffusion in the subcortical white matter on magnetic resonance imaging that is typically observed between 3 and 9 days after illness onset. Here, we report two cases of traumatic head injury with clinical and radiological features similar to those for AESD. The similarities between our cases and AESD may be useful in understanding the pathogenesis of AESD.     

Severe form of acute influenza encephalopathy with biphasic seizures and late reduced diffusion

Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is clinically characterized by biphasic seizures on days 1, and 4 to 6; radiologically by no acute abnormality is visible during the first two days, while reduced diffusion in the subcortical white matter is seen during days 3 to 9, finally resulting in cerebral atrophy. We report here a Japanese child with clinically severe AESD associated with influenza A, whose sequential magnetic resonance imaging revealed cerebral swelling on day 1, reduced diffusion and central herniation on day 6, followed by cortical laminar necrosis and atrophy on day 30. The findings from this patient suggests that AESD has clinically and radiologically a wider spectrum than previously considered.     

Cortical gray matter lesions in acute encephalopathy with febrile convulsive status epilepticus

In acute encephalopathy with febrile convulsive status epilepticus (AEFCSE), subcortical white matter lesions on diffusion-weighted images are sometimes encountered on magnetic resonance imaging (MRI), such as in acute encephalopathy with biphasic seizures and late reduced diffusion (AESD). We report here a severe case of AEFCSE following respiratory syncytial virus infection, with emphasis on the cranial MRI findings. MRI in this patient showed widespread T2-hyperintensity along the cerebral cortical gray matter from day 3 to day 22. Lesions with reduced diffusion were noted on day 3 in the deep zone of gray matter of the left occipito–temporo–parietal cortex, but on day 7 they shifted to the subcortical white matter of both the cerebral hemispheres. These MRI findings provide radiologic evidence for damage to the cortical gray matter in AEFCSE. The serial change of diffusion-weighted images suggests that the cortical gray matter may be injured prior to the involvement of the subcortical white matter.     

Hyperglycemia with occipital seizures: images and visual evoked potentials

PURPOSE: Hyperglycemia may rarely be seen with visual seizures. Observation of both visual evoked potentials (VEPs) and magnetic resonance imaging (MRI) in visual status epilepticus (SE) has not been reported. We describe acute and follow-up VEP and MRI findings of a patient with hyperglycemia-related visual SE of occipital origin. METHODS: In a 59-year-old diabetic woman, complex visual hallucinations and illusions developed with < or =10 seizures per hour as an initial manifestation of nonketotic hyperglycemia. RESULTS: Neurologic examination revealed ictal nystagmus to the right and continuous right hemianopsia. Ictal electroencephalography (EEG) and Tc-99m hexamethylpropylene amine oxime (HMPAO) single-photon emission computed tomography (SPECT) revealed an epileptogenic focus in the left occipital lobe. MRI with fluid-attenuated inversion recovery showed focal subcortical hypointensity and gyral hyperintensity. Follow-up MRI showed only minimal gyral hyperintensity at 6 months. The P100 amplitude of VEP was significantly higher at the right occipital area during SE, but slightly higher on the left after the patient had been seizure free for 6 months. CONCLUSIONS: Occipital seizures and hemianopsia can be caused by hyperglycemia and may be accompanied by special MRI and VEP findings.     

Postictal Subcortical Restricted Diffusion in a Child With Focal Symptomatic Epilepsy

BackgroundDiffusion abnormalities on MRI are well described after prolonged seizures. However, isolated, focal, subcortical restricted diffusion is uncommon.PatientA girl of Kurdish descent experienced focal-onset epilepsy secondary to a left thalamic infarction at age 3 years. At age 6 years, she developed status epilepticus in the context of a febrile illness.ResultsFour days after the seizure, she had neurological deterioration including involuntary posturing movements and irritability. A brain MRI revealed left hemisphere subcortical restricted diffusion, predominantly in the frontal and occipital regions. She experienced persistent right hemiparesis for 2 months after the initial seizure.ConclusionsThis presentation is reminiscent of acute encephalopathy with biphasic seizures and late reduced diffusion, a syndrome thus far reported almost exclusively in Japan. This represents one of the few documented examples of acute encephalopathy with biphasic seizures and late reduced diffusion in an individual not of east Asian descent.     

An unusual case of cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy with occipital lobe involvement

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an autosomal dominant angiopathy caused by a mutation in the notch 3 gene on chromosome 19. Clinically, patients may be asymptomatic or can present with recurrent ischemic episodes and strokes leading to dementia, depression, pseudobulbar palsy, and hemi- or quadraplegia. Additional manifestations that have been described include migraine (mostly with aura), psychiatric disturbances, and epileptic seizures. Neuroimaging is essential to the diagnosis of CADASIL. On imaging CADASIL is characterized by symmetric involvement by confluent lesions located subcortically in the frontal and temporal lobes as well as in the insula, periventricularly, in the centrum semiovale, in the internal and external capsule, basal ganglia, and brain stem; with relative sparing of the fronto-orbital and the occipital subcortical regions. We describe a 49 year old male with CADASIL with absence of temporal lobe findings on MRI but predominant lesions within the periventricular white matter, occipital lobes with extension into the subcortical frontal lobes, corpus callosum and cerebellar white matter. Although CADASIL characteristically presents with anterior temporal lobe involvement, these findings may be absent and our case addresses the atypical imaging findings in CADASIL.     

A case of acute encephalopathy with biphasic seizures and late reduced diffusion: Utility of arterial spin labeling sequence

A 1-year-old boy was admitted because of febrile status epilepticus (FSE). A secondary cluster of seizures was seen on day 5 after onset, and the patient eventually displayed developmental delay. Conventional magnetic resonance imaging (MRI) showed no abnormal findings on day 1 after onset, but showed reduced diffusion in the subcortical regions of bilateral frontal lobes on day 5 after onset. Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) was diagnosed. Arterial spin labeling (ASL) revealed reduced cerebral blood flow (CBF) in bilateral frontal lobes on day 1 after onset and showed increased CBF in the corresponding region in the subacute phase. Outcomes after prolonged febrile seizures are usually good, but mental deficit and/or epilepsy often remain in AESD. Discriminating between these syndromes is difficult, because no useful biomarkers have been identified. Reduced CBF in bilateral frontal lobes was observed on ASL on day 1 of FSE in the present case, and this finding may be predictive of developing AESD.     

Identification of ictal foci by EEG and MR apparent diffusion coefficient map in a case of human herpesvirus 6-associated encephalopathy

We report here a 1-year-old boy with human herpesvirus 6 (HHV 6) -associated encephalopathy. On the 3rd day of fever, he had a generalized tonic seizure followed by mild disturbance of consciousness, which recovered completely the next day. Two days later, he had skin rash of exanthema subitum, and his consciousness declined frequently. EEG demonstrated rhythmic wave bursts originating from central areas bilaterally, followed by a generalized spike-and-wave complex which was associated with disturbed consciousness. We made the diagnosis of a status of complex partial seizures. Because the focal discharge on ictal EEG, MRI was performed. In the subcortical white matter of the frontal-parietal lobes, there were high signals on diffusion-weighted MRI, the apparent diffusion coefficient of which was much lower than that of normal controls. The affected areas soon disappeared with improvement of clinical symptoms. The transient MRI findings may indicate reversible cytotoxic brain edema. He showed no neurological sequelae as yet.     

Serum and cerebrospinal fluid levels of visinin-like protein-1 in acute encephalopathy with biphasic seizures and late reduced diffusion

Background: Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) has recently been recognized as an encephalopathy subtype. Typical clinical symptoms of AESD are biphasic seizures, and MRI findings show reduced subcortical diffusion during clustering seizures with unconsciousness after the acute phase. Visinin-like protein-1 (VILIP-1) is a recently discovered protein that is abundant in the central nervous system, and some reports have shown that VILIP-1 may be a prognostic biomarker of conditions such as Alzheimer’s disease, stroke, and brain injury. Methods: However, there have been no reports regarding serum and cerebrospinal fluid (CSF) levels of VILIP-1 in patients with AESD. We measured the serum and CSF levels of VILIP-1 in patients with AESD, and compared the levels to those in patients with prolonged febrile seizures (FS). Results: Both serum and CSF levels of VILIP-1 were significantly higher in patients with AESD than in patients with prolonged FS. Serum and CSF VILIP-1 levels were normal on day 1 of AESD. Conclusions: Our results suggest that both serum and CSF levels of VILIP-1 may be one of predictive markers of AESD.     

Acute encephalopathy with biphasic seizures and late reduced diffusion: Predictive EEG findings

BackgroundAcute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is a common type of acute encephalopathy in Japan; the condition is clinically characterized by prolonged seizures as the initial neurological symptom, followed by late seizures 4–6 days later. It is difficult to differentiate AESD from prolonged febrile seizures (PFSs). Here, we explored the use of electroencephalography to differentiate AESD from PFSs.MethodsWe studied the electroencephalograms (EEGs) of children <6 years of age diagnosed with AESD or PFSs; all EEGs were recorded within 48 h of seizure onset (i.e., before the late seizures of AESD). Two pediatric neurologists evaluated all EEGs, focusing on the basic rhythm, slowing during wakefulness/arousal by stimuli, spindles, fast waves, and slowing during sleep.ResultsThe EEGs of 14 children with AESD and 31 children with PFSs were evaluated. Spindles were more commonly reduced or absent in children with AESD than in those with PFSs (71% vs. 31%, p = 0.021). Fast waves were also more commonly reduced or absent in children with AESD (21% vs. 0%, p = 0.030). The rates of all types of slowing did not differ between children with AESD and those with PFSs, but continuous or frequent slowing during sleep was more common in the former (50% vs. 17%, p = 0.035).ConclusionsEEG findings may usefully differentiate AESD from PFSs. Reduced or absent spindles/fast waves and continuous or frequent slowing during sleep are suggestive of AESD in children with prolonged seizures associated with fever.     

A 59-year-old woman with recurrent convulsive seizures, cerebral infarctions, dementia, and intracranial calcifications]

A 59-year-old woman with recurrent seizures and progressive dementia is reported. Her past history and familial history were unremarkable. She became short-tempered at 56 years old (Oct. 1991). She had the first seizure attack and was admitted to a hospital at March 4, 1993, with prolonged disturbance of consciousness and subsequent mental deterioration. Her brain CT showed multiple small calcifications in the subcortical white matter and pons. The laboratory data including blood count, serum chemistry, serological studies and CSF was normal. MRI and digital subtraction angiography of the cranial vessels were unremarkable. There was a decrease in accumulation in the right cerebral hemisphere on 123I IMP SPECT. Despite anti-convulsant therapy, she had recurrent seizures several times, with gradual worsening of her mental state. She had the latest seizure attack and was transferred to Matsusaka Chuo Hospital, on August 29, 1993. After the attack she had been in the apallic state, and died on Nov. 13, 1995. This case was discussed in a neurological CPC. The discussants suggested that the isolated angiitis of the central nervous system caused secondary seizures and cerebral infarctions. Post-mortem examination revealed the CNS findings of vasculitis at various stages, calcification or mineralization mainly in the subcortical white matter and pons, massive cerebral infarctions with massive exudate, fresh and old small bleedings and exudate around the inflamed or calcified vessels. The white matter degeneration resembled that of Binswanger leukoencephalopathy. The final pathological diagnosis was isolated angiitis of the central nervous system since there was no inflammatory changes or atherosclerotic change of the blood vessels in the extracranial organs.     

Alexia without agraphia in multiple sclerosis: case report with magnetic resonance imaging localization

The syndrome of alexia without agraphia occurs rarely in multiple sclerosis (MS). We report a patient with right homonymous hemianopsia and alexia without agraphia as his initial manifestations of relapsing-remitting MS. Magnetic resonance imaging (MRI) demonstrated a hyperintense lesion in the left occipital subcortical white matter (WM) and an enhancing lesion in the splenium of the corpus callosum. The clinical presentation and MRI findings were consistent with disconnection of the functional right occipital visual cortex from structures responsible for language comprehension in the left hemisphere. The diagnosis of MS was confirmed by subsequent development of additional periventricular WM lesions.     

White matter density is increased in patients with hypothalamic hamartoma and multiple seizure types

Many patients with hypothalamic hamartomas present in infancy with gelastic seizures of subcortical origin, but later develop additional seizure types, including complex partial, tonic, and generalized tonic-clonic seizures. The basic cellular mechanisms responsible for this evolution in seizure types are unknown. Using voxel-based morphometry of T1 weighted MRI scans we compared eight patients with only gelastic seizures with 16 age-matched patients with multiple seizure types and found significantly greater white matter density in the temporal lobes and cerebellum in those with multiple seizure types. This suggests that increased white matter density, perhaps resulting from maturational changes and resulting in increased brain connectivity, is associated with a higher likelihood of cortical involvement in epilepsy resulting from hypothalamic hamartoma.     

Celiac Disease, Bilateral Occipital Calcifications and Intractable Epilepsy: Mechanisms of Seizure Origin

Summary: Purpose: To elucidate the mechanisms of seizure origin in patients with celiac disease and bilateral occipital calcifications (CEBOC). Individuals with CEBOC frequently present with occipital lobe seizures, but additional lesions and additional attack patterns may occur.
Methods: We studied two men and one woman who had CEBOC. Villous atrophy was revealed in the two patients who underwent duodenal biopsy. All had a comprehensive presurgical evaluation, including prolonged video-EEG recordings. Two had magnetic resonance imaging (MRI) with volumetric study of mesial temporal structures (MRIV). One patient had undergone stereotactic intracranial depth electrode studies (SEEG).
Results: All patients presented with intractable complex partial seizures. Two had partial simple seizures with visual aura. Neurologic examination was normal; one was of normal intelligence, and two were mildly retarded. Neuroimaging studies showed that each had bilateral occipital calcifications as well as epileptiform abnormalities over temporal lobes. In one, MRI showed an additional right frontal lesion, but SEEG demonstrated right occipital lobe seizure origin with anterior spread; this male patient later underwent a right occipital lobe resection. Another with a history of prolonged febrile convulsions had bilateral hippocampal and amygdalar atrophy demonstrated by MRIV.
Conclusions: In one patient, SEEG confirmed that seizures originated in the occipital lobe. The presence of dual pathology was demonstrated in another, raising the possibility of both occipital and temporal seizure onset. The presence of extraoccipital lesions or of mesial temporal atrophy requires SEEG for clarification of seizure onset. In the absence of confounding factors and when laterality can be demonstrated, surgical treatment may be considered.     

Occipital lobe epilepsy: clinical characteristics, seizure spread patterns, and results of surgery.

Twenty-five patients with occipital lobe seizure origin were retrospectively evaluated to determine clinical seizure characteristics and electroencephalographic manifestations. Certain symptoms and signs served to identify occipital lobe origin in 22 (88%). These included elementary visual hallucinations, ictal amaurosis, eye movement sensations, early forced blinking or eyelid flutter, and visual field deficits. Eye or head deviation, or both, was observed frequently and was contralateral to the side of seizure origin in 13, but 3 patients exhibited ipsilateral deviation in some or all their seizures. After the initial signs and symptoms, clinical seizure characteristics resembled those of seizures originating elsewhere. Seizures typical of temporal lobe origin with loss of contact and various types of automatic, semipurposeful activity occurred in 11 patients. Seizures in 3 patients exhibited asymmetrical tonic or focal clonic motor patterns characteristic of frontal lobe seizures. Eleven of the 25 patients had, on two occasions, two or more distinctly different seizure types. Scalp electroencephalographic findings were seldom helpful for occipital lobe localization and were frequently misleading. Intracranial electroencephalographic recording correctly identified occipital lobe seizure origin in most, but not all, patients who had such studies. Intracranial electroencephalic recording also proved the variability in clinical seizure characteristics was related to different seizure spread patterns, medially or laterally above and below the sylvian fissure, both ipsilateral and contralateral to the occipital lobe of seizure origin. Eighteen patients had occipital lobe lesions detected with computed tomographic or magnetic resonance imaging scans or both. Resection of the lesions in 16 patients produced excellent results in 14 (88%). Five patients had temporal lobectomies, with good results in 3, but poor results in 2. Two patients with unlocalized seizures had complete section of the corpus callosum, 1 with a good result and the other with a poor result.     

Clinical and Magnetic Resonance Imaging Regression of Progressive Multifocal Leukoencephalopathy in an AIDS Patient After Intensive Antiretroviral Therapy

A 36-year-old homosexual man with 6 months of visual symptoms and headaches had right homonymous hemianopia, mild new learning impairment, and alexia with agraphia. The initial brain magnetic resonance imaging (MRI) scan was reported consistent with left occipital infarction. Subsequent MRI demonstrated abnormal demyelination in subcortical white matter and deep parieto-occipital white matter bilaterally, but primarily left. Human immunodeficiency virus testing and cerebrospinal fluid polymerase chain reaction for JC virus DNA were both positive, consistent with progressive multifocal leukoencephalopathy (PML) with AIDS. His clinical status steadily deteriorated, and MRI white matter abnormalities worsened despite high-dose antiretroviral therapy. After the antiretroviral regimen was intensified by the addition of a protease inhibitor, rapid clinical and radiographic improvement occurred with subsequent MRI studies revealing only residual left parieto-occipital encephalomalacia. PML in AIDS patients has been associated with a nearly uniformly poor prognosis until recent reports of improved outcomes after highly active antiretroviral therapy. This patient with PML and AIDS similarly showed a robust clinical and MRI response to intensive antiretroviral combination therapy, which has been maintained for more than 3 years.