Acute necrotizing encephalopathy associated with enterovirus infection

Acute necrotizing encephalopathy is a rare, clinically distinct entity of acute encephalopathy triggered by acute febrile diseases, mostly viral infections. It is postulated to arise from uncontrolled cytokine release during a febrile illness, and is most often seen in East Asia. We describe a rare Saudi patient of acute necrotizing encephalopathy attributable to enterovirus in a 4 years and 6 months old girl. A work-up revealed elevations in serum and cerebrospinal fluid interleukin-6 and tumor necrosis factor-α. The outcome on intravenous pulse methylprednisolone was good. This case is the first, to the best of our knowledge, of acute necrotizing encephalopathy reported from Saudi Arabia with a good outcome despite severe magnetic resonance imaging findings and delay in the steroid treatment.     

Acute necrotizing encephalopathy associated with hemophagocytic syndrome

A 7-year-old female suddenly exhibited high fever and convulsions, and entered a semi-coma. She also had thrombocytopenia, elevated aminotransferase, prolonged prothrombin time and activated partial thromboplastin time, and hemophagocytes in the bone marrow. The brain magnetic resonance imaging revealed multiple low-intensity areas on the T1-weighted images, and high-intensity areas on the T2-weighted images bilaterally in the thalamus, the dorsal part of the pons, and the cerebellar white matter. The patient was diagnosed as having both acute necrotizing encephalopathy and hemophagocytic syndrome. Serum and cerebrospinal fluid interleukin-6 and tumor necrosis factor-alpha were elevated to the same high levels (serum:cerebrospinal fluid interleukin-6, 103:101 pg/mL; tumor necrosis factor-alpha 753:753 pg/mL). The clinical symptoms and the magnetic resonance imaging findings improved immediately after the administration of dexamethasone. These results suggest that the hypercytokinemia and the hyperpermeability of both the blood-brain barrier and the capillary walls of the central nervous system might be essential in the pathogenesis of acute necrotizing encephalopathy, and that early steroid therapy might be effective in these conditions.     

Acute necrotizing encephalopathy associated with human herpesvirus-6 infection

An extremely rare case of acute necrotizing encephalopathy caused by human herpesvirus-6 variant type B infection is reported. The patient, a 14-month-old previously healthy female, presented with high fever and generalized tonic convulsion followed by rapid deterioration of consciousness. On the second day of the illness, the protein level of the cerebrospinal fluid increased without pleocytosis. On the third day, magnetic resonance images demonstrated symmetric, abnormal signal intensity lesions in the bilateral thalamus, cerebellum, and brainstem. On the fourth day, characteristic maculopapular rash of exanthema subitum appeared on the trunk. Human herpesvirus-6 deoxyribonucleic acid was detected by the polymerase chain reaction in the serum, and immunoglobulin G and immunoglobulin M of serum human herpesvirus-6 were positive. On the twelfth day of illness, the patient died as a result of severe brain damage. Acute necrotizing encephalopathy should be included in the differential diagnosis when examining infants and young children with fulminating consciousness disturbance and intractable convulsion. In addition, as a causative virus, human herpesvirus-6 has to be considered at the pre-eruptive stage of exanthema subitum. Magnetic resonance images are useful because they reveal the characteristic distribution of lesions specific to acute necrotizing encephalopathy.     

Acute necrotizing encephalopathy of childhood associated with influenza type B virus infection in a 3-year-old girl

Acute necrotizing encephalopathy of childhood represents a novel entity of acute encephalophathy, predominantly affecting infants and young children living in Taiwan and Japan. It manifests with symptoms of coma, convulsions, and hyperpyrexia after 2 to 4 days of respiratory tract infections in previously healthy children. The hallmark of acute necrotizing encephalopathy of childhood consists of multifocal and symmetric brain lesions affecting the bilateral thalami, brainstem tegmentum, cerebral periventricular white matter, or cerebellar medulla. The etiology and pathogenesis of this kind of acute encephalopathy remain unknown, and there is no specific therapy or prevention. The prognosis is usually poor, and less than 10% of patients recover completely. We report a 3-year-old previously healthy girl presenting with acute necrotizing encephalopathy of childhood associated with influenza type B virus infection, which resulted in severe neurologic sequelae. We also review the current knowledge of the clinical, neuroimaging, and pathologic aspects of acute necrotizing encephalopathy of childhood.     

Acute disseminated encephalomyelitis associated with parainfluenza virus infection of childhood

Acute disseminated encephalomyelitis associated with the parainfluenza virus has rarely been reported in childhood. A 2.5-year-old girl with acute disseminated encephalomyelitis, who developed bilateral symmetrical lesions in the basal ganglion, thalamus, corpus callosum, cerebral subcortical white matter, and cerebellar medulla on brain magnetic resonance imaging is described. Serological confirmation of parainfluenza virus infection was made 2 weeks following the onset of neurological symptoms. Four months later, the patient had a full recovery. At present, 3 years later, no relapse has been reported and she is leading a normal life. Our case is of interest because of its rarity, the striking brain magnetic resonance imaging, and the good neurological outcome.     

Favorable outcomes in acute necrotizing encephalopathy in a child treated with hypothermia

Acute necrotizing encephalopathy predominately affects young children in Japan, Taiwan, and Korea. It manifests with fever, altered mental status, and seizures 2-5 days after the onset of upper respiratory infection. It is commonly associated with influenzas A, B, and H1N1. The hallmark of the encephalopathy involves multifocal, symmetric brain lesions affecting the bilateral thalami, brainstem tegmentum, cerebral periventricular white matter, cerebellum, and medulla, as visualized by computed tomography and magnetic resonance imaging. Prognoses were uniformly dismal before 1980, with high mortality rates and severe neurologic sequelae in survivors. We describe a previously healthy 4-year-old Caucasian girl who presented with fever, alterations of consciousness, and convulsions. Nasal swab revealed her to be influenza A-positive, and her magnetic resonance imaging was diagnostic of the disease. Prompt recognition of the disease and treatment with hypothermia and anti-inflammatory agents led to a favorable outcome.     

Acute relapsing encephalopathy mimicking acute necrotizing encephalopathy in a 4-year-old boy

A 4-year-old boy showed two episodes of encephalitis/encephalopathy involving disturbed consciousness, convulsion, and paresis associated with the elevated levels of protein and myelin basic protein of the cerebrospinal fluid. MRI studies of the brain revealed symmetrical lesions in the brain stem and thalami at the first episode, and additional lesions were found in the cerebellum involving both the gray and white matter in the second episode. The intensities of MRI lesions were low in T1 and high in T2. These episodes were followed by an elevation of the anti-viral antibody titers, for influenza A virus during the first episode and for adenovirus during the second. In the second episode, intravenous methylprednisolone therapy resulted in rapid improvement of his neurological signs.     

EEG findings in a case of acute necrotizing encephalopathy of childhood associated with influenza A virus infection

We reported here a case of symptomatic partial epilepsy following acute necrotizing encephalopathy of childhood associated with influenza A virus infection. This 2-year-old boy underwent repeated EEG recordings, which at the acute stage was dominated by diffuse 1-2 Hz slow waves. The background activity was 5 Hz theta waves on the 49th day. Paroxysmal activities appeared after the 89th day of illness. On the 231st day, EEG showed spike-and-waves on the left and right frontal areas. Interestingly, paroxysmal activities preceded the onset of epileptic seizures by 7 months, and spike-and-waves by 2 months. After 10 months, he had generalized seizures with fever, and partial seizures on awakening without fever. Interictal EEG showed spike-and-waves on the bilateral frontal areas, and diffuse polyspikes and slow waves were occasionally seen. Though the background activity improved, his consciousness level did not recover probably because the thalamus, basal ganglia, brainstem were damaged more severely than the cerebral cortex.     

Acute encephalopathy associated with vigabatrin in a six-month-old girl

Summary: Purpose: Vigabatrin (VGB) is a new‐generation anticonvulsant used in the treatment of partial seizures and West syndrome. Side effects of VGB treatment in adults and children are well described. Acute encephalopathy with VGB has recently been reported in eight adults. They developed stupor, confusion, and electroencephalographic abnormalities after starting VGB. Does the acute encephalopathy with VGB also occur in childhood? Methods: We describe a 6‐month‐old girl with infantile Alexander disease with hydrocephalus who developed similar clinical symptoms with apathia, somnolence, and sopor, as well as slowing of the background activity in EEG, 3 days after starting VGB. After exclusion of shunt dysfunction, encephalitis, metabolic dysfunction, and renal failure, VGB was discontinued. Results: During the next 2 days, symptoms subsided, and after 10 days, EEG background activity returned to the one before starting VGB. Conclusions: Acute encephalopathy associated with VGB in children seems to be very rare, but should not be ignored.     

Acute necrotizing encephalopathy due to SARS-CoV-2 in a pregnant female

Neurological Sciences -     

Acute necrotizing encephalopathy presenting as a basal ganglia syndrome.

Acute necrotizing encephalopathy is a relatively new disease. The characteristic clinical findings are of febrile illness followed by rapid deterioration in mental status and seizures. The hallmark of the disease is multifocal bilateral symmetric lesions affecting the thalamus, hypothalamus, brainstem tegmentum, cerebral white matter, and cerebellum. The etiology is unknown, but immune-mediated mechanism was suggested. We present a 12-year-old previously healthy girl who developed increased sleepiness progressing to stupor and coma. Magnetic resonance imaging (MRI) of the brain showed the characteristic findings previously described in acute necrotizing encephalopathy. Her mental status improved dramatically with steroid treatment, and the MRI findings resolved completely within 6 months. Following the acute illness, she developed a complex neuropsychiatric disorder consistent with basal ganglia syndrome.     

Acute necrotizing encephalopathy with widespread edematous lesions of symmetrical distribution

Summary A 67-year-old Japanese woman with liver cirrhosis was affected by an unusual acute progressive encephalopathy, presenting mental confusion and slurred speech as its initial symptoms. She died in profound coma, following the entire course of 17 days. Autopsy disclosed bilateral symmetrical, widespread, edematous and necrotic lesions, their centers being located in the basal ganglia, diencephalon and midbrain, and their peripheries expanding into the cerebral white matter, cerebellum, pons and medulla. Diapedesis of erythrocytes and serum plasma was conspicuous, in contrast to paucity of capillary proliferation. Although the lesions were somewhat similar to those of Wernicke's and Leigh's encephalopathies, they were considered to be representative of a more acute metabolic disorder distinct from the latter conditions.