Infantile bilateral striatal necrosis

Summary A case of infantile bilateral striatal necrosis (IBSN) is reported, the first one found in Scandinavia. Extensive clinical and laboratory investigations did not reveal any evidence of a neurometabolic disease. By computed tomography (CT) degeneration of putamen of either side was detected. The neuropathologic findings included extensive bilateral destruction of the striatum and pallidum and degeneration of the substantia nigra and tegmental nuclei. In the damaged regions, accumulations of cells containing sudanophilic lipids were found and Alzheimer type II glial cells, which were also seen in the cortex. On the basis of the clinical picture and the destruction of nerve cells in particular areas of the brain, in the present case and previously published cases of IBSN, the possible role of glutamatc and other excitotoxic transmitters in the pathogenesis of the disease is discussed.Supported by a grant from Expressens fond för perinatalforskning     

Familial infantile bilateral striatal necrosis: clinical features and response to biotin treatment

BACKGROUND: Infantile bilateral striatal necrosis (IBSN) encompasses several syndromes of bilateral symmetric, spongy degeneration of the caudate nucleus, putamen, and globus pallidus. The familial form of IBSN is rare, and inheritance is either autosomal recessive or maternal. METHOD: The authors describe an Israeli Bedouin kindred in which 15 children born to consanguineous parents were affected with familial IBSN. They evaluated the clinical and radiologic evolution of the disease in 11 patients and the cerebral pathologic findings in one patient. Three of the children were treated with oral biotin 100 mg/day. RESULTS: Inheritance was apparently autosomal recessive. The untreated children had a similar clinical picture including developmental arrest beginning at the age of 7 to 15 months, choreoathetosis, and dysphagia. Pendular nystagmus appeared at a late stage. MRI, performed at various stages of the disease, showed severe basal ganglia atrophy. Postmortem study in one patient showed severe atrophy of the lenticular nuclei with gliosis and loss of neurons. Biotin, 100 mg/day, administered to the proband over a period of 15 months, may have slowed progression. In two other children treatment was initiated earlier and appeared to arrest or improve disease. CONCLUSIONS: Familial infantile bilateral striatal necrosis was inherited as an autosomal recessive trait. Clinical features included developmental arrest, dysphagia, and choreoathetosis. Imaging and pathology showed atrophy and degeneration of the basal ganglia. Oral biotin may have benefited three children.     

Infantile bilateral striatal necrosis following measles

A previously healthy 4-year-old boy presented with typical measles and demonstrated lesions confined to basal ganglia. The clinical symptoms were an abrupt onset, impaired consciousness and mutism, extrapyramidal signs and severe neurovegetative dysfunction. No modification of the cerebrospinal fluid was observed; laboratory tests were all normal with the exception of a positive serologic test for measles. Cranial magnetic resonance imaging showed abnormal signals in the striatum, affecting the putamen and the caudate nuclei bilaterally. Neurologic improvement occurred within 2 months, with regression of lesions on cranial imaging, suggesting that edema played an important role in the initial stage of the disease.     

Reversible parainfectious bilateral "striatal necrosis"

Bilateral striatal necrosis is usually associated with either endogenous or exogenous toxins, and with poor neurodevelopmental outcomes. We describe two patients with acute bilateral striatal clinical syndrome and magnetic resonance signal changes who made a complete clinical and radiologic recovery within 3 months. After an uneventful pregnancy, normal birth, and normal development, both boys presented at ages 3 and 5 years, respectively, after a viral illness with slurring of speech, bradykinesia, and an extrapyramidal movement disorder. On examination, both manifested bilateral cog wheel rigidity, with a broad-based gait and flexor plantar response. Cranial magnetic resonance imaging in both children indicated bilateral, symmetric, high signal changes in the lentiform nucleus, predominately in the putamen, with sparing of the globus pallidi bilaterally. The brain parenchyma was otherwise normal. Neurometabolic investigations produced normal results in both patients. The pathogenesis is uncertain, but could be immune-mediated. Both children, at 3-year and 1-year follow-ups, respectively, are doing well neurologically and academically. Our patients demonstrate that abnormal imaging findings during acute stages do not preclude good clinical and radiologic recovery.     

Infantile bilateral striatal necrosis. Clinicopathological classification

Two cases of infantile bilateral striatal necrosis (IBSN) were studied retrospectively, and the literature was reviewed. The two children had presented with progressive neurologic signs of involuntary movements or muscle hypertonia from infancy. Initial computed tomography scans showed mild atrophy of the caudate nuclei or basal ganglia, and the neuropathologic examination revealed diffuse neuronal loss with some patchy preservation and marked astrogliosis in the striatum and globus pallidus. The 27 reported cases of IBSN were divided into three groups with characteristic clinical and pathologic features: early, acute onset (four cases); early, gradual onset (16 cases); and late onset (seven cases). Although metabolic changes in the developing corpus striatum may be important in the pathogenesis of IBSN, the origin is uncertain.     

Acute infantile bilateral striatal necrosis: single-photon emission computed tomography (SPECT) imaging and review

Acute infantile bilateral striatal necrosis is a rarely described acute neurological syndrome associated with radiological findings. Its etiology and pathogenic mechanisms are unknown. Clinically, the syndrome usually follows respiratory illnesses and presents with an array of neurological findings, including axial ataxia, grimacing, mutism, head nodding, and high-pitched cry. This study follows a child with acute infantile bilateral striatal necrosis both clinically and radiologically. In addition, for the first time, the authors describe the serial findings of single-photon emission computed tomography (SPECT) from onset of illness through 20 months. Their findings indicate an initial insult apparent on both magnetic resonance imaging and SPECT localized to the basal ganglia, which, although improved over time, does not fully regress. The residual lesion on SPECT was clinically associated with only mild attention deficit disorder and no motor pathology. The authors review the published literature concerning acute infantile bilateral striatal necrosis and suggest possible mechanisms of this poorly understood and probably underreported condition.     

Post-streptococcal autoimmune dystonia with isolated bilateral striatal necrosis

Infantile bilateral striatal necrosis (IBSN) is characterized by a dystonic movement disorder and basal ganglia imaging abnormalities. Acute IBSN often occurs after upper respiratory tract infections although no specific micro-organism which may cause IBSN has been identified. We present 2 children (1 year 2 months and 4 years) with acute IBSN after clinical pharyngitis. Both IBSN patients had serological evidence of recent beta-haemolytic streptococcal infection. Due to the association of post-streptococcal disorders with anti-basal ganglia antibodies (ABGA), we examined both patients for anti-neuronal antibodies. For comparison, 20 children with dystonia (9 females, 11 males; mean age 4 years 1 month), and 20 children with uncomplicated streptococcal infection (12 females, 8 males; mean age 5 years 9 months) were examined. Both IBSN patients had antibodies reactive against basal ganglia constituents of molecular weight 40 kDa. Immunohistochemistry showed antibody reactivity against large striatal neurons only. Other anti-neuronal antibodies were negative, supporting striatal specificity. All controls were negative for ABGA. Acute IBSN is part of the poststreptococcal autoimmune neuropsychiatric spectrum. An autoimmune aetiology should be considered in this phenotype, as immunomodulatory therapies may reduce morbidity and mortality.     

Mutations in TNK2 in severe autosomal recessive infantile onset epilepsy

We identified a small family with autosomal recessive, infantile onset epilepsy and intellectual disability. Exome sequencing identified a homozygous missense variant in the gene TNK2, encoding a brain‐expressed tyrosine kinase. Sequencing of the coding region of TNK2 in 110 patients with a similar phenotype failed to detect further homozygote or compound heterozygote mutations. Pathogenicity of the variant is supported by the results of our functional studies, which demonstrated that the variant abolishes NEDD4 binding to TNK2, preventing its degradation after epidermal growth factor stimulation. Definitive proof of pathogenicity will require confirmation in unrelated patients. Ann Neurol 2013;74:496–501     

A case report of infantile striatal necrosis with an acute onset

We report here an autopsy case, an 8-year-old boy diagnosed as having infantile striatal necrosis, characterized by a preceding febrile illness followed by acute encephalopathy with abrupt obtundation, seizures and dystonia, with remarkable improvement of the disturbed consciousness and intelligence after TRH-T therapy. These clinical symptoms were linked with bilateral necrosis of the striata on CT scanning. The presented case belonged to a newly described subgroup of the heredogenous disorders that produce necrosis of the putamina in children.     

Acute bilateral striatal necrosis with rotavirus gastroenteritis and inborn metabolic predisposition

We present a 9-month-old male with acute rotavirus gastroenteritis who developed an acute encephalopathy with focal seizures and developmental regression. Magnetic resonance imaging showed bilateral striatal necrosis and raised glutarylcarnitine levels on tandem mass spectrometry of a (crisis) blood spot, and chromatography of organic acids revealed increased urinary excretion of dicarboxylic acid. Skin biopsy demonstrated a partial decrease in glutaryl-CoA dehydrogenase activity. The case was not typical for either rotavirus encephalitis/rotavirus-associated encephalopathy or for glutaric aciduria type I. The patient has developmental delay and continues to receive physiotherapy, speech therapy, and local developmental follow-up.     

A case of bilateral striatal necrosis associated with vesicular skin eruption

We report here a case of bilateral striatal necrosis associated with vesicular eruption in the generalized skin. A 13-year-old, previously healthy boy had a febrile disease which was treated with antibiotics, anti-inflammatory drugs, and an antiemetic agent. Two days later, generalized vesicular rash appeared. Seven days later, he became dysarthric. Rigidity and paralysis of the legs also developed, followed by mild disturbance of consciousness. Despite treatment with high-dose methylprednisolone and L-dopa, neurological symptoms worsened after admission, with appearance of involuntary movements and dysphagia. One month later, however, they improved spontaneously, and the patient was discharged with minimal sequelae. Cranial magnetic resonance imaging (MRI) demonstrated high signal intensity lesions in the bilateral striatum on both the T1- and T2-weighted images. The dermatologic and neurologic disorders of this case may have resulted from drug allergy, although role of the infection was not excluded completely. The MRI findings may reflect microhemorrhage or necrosis in the striatal lesions.     

Familial infantile myoclonic epilepsy: clinical features in a large kindred with autosomal recessive inheritance

PURPOSE: To describe the clinical features of a large kindred with familial infantile myoclonic epilepsy (FIME) with autosomal recessive inheritance, and to discuss the nosology of the early infantile myoclonic epilepsies (IMEs). METHODS: The family descends from the intermarriage of two couples of siblings. In a previous study, we mapped the genetic locus to chromosome 16p13.We analyzed results of family records and personal history, psychomotor development, neurologic examination, epilepsy features, and EEG recordings for each subject. RESULTS: FIME has a strong penetrance (eight affected of 14 subjects) and a homogeneous clinical picture. Like the benign form of infantile myoclonic epilepsy (BIME), FIME is a true idiopathic IME with unremarkable history, no neurologic or mental impairment, good response to treatment, and normal interictal EEG pattern. Conversely, onset with generalized epileptic seizures without fever (four patients) or with fever (one patient), frequency and duration of the myoclonic seizures, occurrence of generalized tonic--clonic seizures (GTCSs) in all patients and persistence of seizures into adulthood are characteristics of the severe infantile myoclonic epilepsy (SIME). CONCLUSIONS: Clinical overlap probably exists among the myoclonic epilepsies of infancy. FIME differs from other forms of IME in its phenotypic features. The peculiar mode of inheritance is explained by the genetic background of the family. Genetic studies suggest linkage to chromosome 16 in familial cases of true IME.     

A novel mitochondrial ATPase 6 point mutation in familial bilateral striatal necrosis

A T-to-C transition at nucleotide (nt) 9176 in the mitochondrial adenosine triphosphatase 6 (ATPase 6) gene was detected in 2 brothers with a neurological disorder resembling Leigh syndrome. The mutation was also present in the 2 other siblings and in the mother, who were asymptomatic. In the more severely affected boy (the proband), the mutation was homoplasmic in muscle, leucocytes, and fibroblasts. In leucocytes from his affected brother, 98% of mtDNA was mutant. Heteroplasmy of varying degrees was seen in leucocytes from the mother and the 2 unaffected siblings. The mutation changes a highly conserved leucine residue near the carboxyl terminus of the mitochondrial ATPase 6 subunit to proline. It could not be detected in 168 control subjects. Studies of ATP synthesis and hydrolysis in fibroblasts from the proband were normal.     

Acute encephalopathy with bilateral striatal necrosis. A distinctive clinicopathological condition.

Two patients with acute encephalopathy with bilateral striatal necrosis are presented and the literature on the subject is reviewed. The disease is characterized by abrupt onset following a systemic infectious illness, with disturbance of consciousness, absence of speech, dystonic movements of the limbs, general stiffness, opisthotonus, tremor, facial grimacing, and stereotyped reaction to painful stimuli. After a variable period of time, there is gradual improvement of the neurological status with clearing of consciousness and recovery of motor functions. Mild CSF pleocytosis is the only abnormal laboratory test encountered. Cranial imaging shows from the beginning of the illness, bilateral involvement of the striatum that may persist indefinitely. The pathogenesis of this disorder remains unknown although an infectious or para-infectious mechanism seems to be the most likely possibility.     

Transient seizure disappearance due to bilateral striatal necrosis in a patient with intractable epilepsy

An 8-year-old girl had suffered from intractable epilepsy due to cortical dysplasia. She developed mycoplasma pneumonia with massive pleural effusion. Fever continued for 3 weeks. Four weeks after the onset of this infection, she suddenly developed horizontal nystagmus, ataxia, choreoathetotic movements and confusion. CT disclosed swelling and low density of the heads of the caudate nuclei and putamina bilaterally. MRI revealed areas of symmetrical high intensity in the striatum on T2-weighted imaging. These lesions were thought to comprise bilateral striatal necrosis (BSN) mediated by the mycoplasma infection or Wernicke encephalopathy. Six months later, she had completely recovered clinically. During the 6 months after BSN, she did not have any epileptic seizures. Her epileptic seizures reappeared thereafter at a lower frequency. The striatum may be involved in the propagation pathway for epileptic seizure activity in this patient.     

SLC25A19 mutation as a cause of neuropathy and bilateral striatal necrosis

Four patients, aged 7–20 years, suffered from recurrent episodes of flaccid paralysis and encephalopathy associated with bilateral striatal necrosis and chronic progressive polyneuropathy. Using homozygosity mapping, a pathogenic missense mutation in the SLC25A19 gene that encodes the mitochondrial thiamine pyrophosphate transporter was identified. An SLC25A19 mutation was previously reported in Amish congenital lethal microcephaly but the present patients' phenotype is markedly different, with normal head circumference, normal early childhood development, age‐appropriate cognitive skills, and normal urinary organic acid profile. Determination of the SLC25A19 sequence should be considered in patients with bilateral striatal necrosis and progressive polyneuropathy. Ann Neurol 2009;66:419–424     

Infantile bilateral striatal necrosis associated with human herpes virus-6 (HHV-6) infection

A 1-year-old female with acute bilateral striatal necrosis secondary to exanthema subitum associated with human herpesvirus 6 (HHV-6) infection is reported. The patient was previously healthy. She presented with progressive neurologic signs of oral dyskinesia and involuntary movements, after suffering from exanthema subitum. Initial magnetic resonance imaging (MRI) demonstrated abnormal signals in the bilateral striatal regions. In addition, the serum HHV-6 IgM class antibody level was significantly increased. The patient is thought to be the first case of HHV-6 infection related infantile bilateral striatal necrosis (IBSN).