Calcification of the basal ganglia: computerized tomography and clinical correlation

During a 1-year period, 4219 consecutive computerized tomograms (CT) were reviewed for basal ganglia calcification; 14 patients with such calcification were identified. Calcifications on CT scan were bilateral in 12 of these cases and unilateral in 2. All bilateral calcifications were symmetric. The globus pallidus was the site of calcification in 13 of the 14 patients. Bilateral dentate nucleus calcification was seen in one patient. Skull radiograms were normal in all but one. Patients had diverse symptoms that were often explained by other findings, suggesting that calcifications may be coincidental and that basal ganglia calcification may not be a nosologic entity. Disturbances of calcium metabolism were not found in these patients, minimizing the pathophysiologic significance of altered calcium metabolism and the need for extensive endocrinologic evaluation. The finding of basal ganglia calcification alone does not justify invasive diagnostic procedures. Extrapyramidal signs may be associated with basal ganglia calcification; parkinsonism associated with basal ganglia calcification differs from idiopathic parkinsonism in being resistant to levodopa therapy.     

HOMOCARNOSINOSIS. 3 SPINAL FLUID AMINO ACIDS IN FAMILIAL SPASTIC PARAPLEGIA

Increased concentration of CSF homocarnosine has recently been found in a family with spastic paraplegia. CSF homocarnosine was therefore determined in 13 patients from other families with familial spastic paraplegia. Also examined were seven patients from families where the constellation of symptoms and signs was more complex, but also comprised spastic paraplegia, and five patients with non-familial spastic paraplegia. No changes were found in homocarnosine level. In one patient with spastic familial paraplegia clear elevation of threonine in the CSF was found. The affected brother showed no such abnormality. CSF homocarnosine elevation is thus no common denominator in familial spastic paraplegia.     

Restricted unilateral Sydenham's chorea: reversible contralateral striatal hypermetabolism demonstrated on single photon emission computed tomographic scanning.

Sydenham's chorea results from group A streptococcus infection and subsequent generation of antineuronal antibodies directed at the caudate nucleus and putamen. Predominantly bilateral, in up to 30% of cases the chorea can be unilaterally restricted. Imaging studies, both structural (magnetic resonance imaging) and functional (positron emission tomography), in patients with bilateral Sydenham's chorea have suggested reversible striatal abnormalities. Two patients with unilateral Sydenham's chorea are presented. Computed tomographic and magnetic resonance imaging were normal in both. However, hexamethylpropylenamine oxime single photon emission tomographic (HMPAO SPECT) studies demonstrated hypermetabolism in the contralateral basal ganglia. Resolution of symptoms in one of the patients coincided with normalization of the SPECT scan. Thus, unilateral striatal hypermetabolism appears to underlie the contralateral chorea observed. A SPECT scan probably should be included in the work-up of new-onset chorea.     

Benign essential tremor. A clinical survey of 82 patients from Campania, a region of southern Italy

We report a clinical survey of 82 patients with benign essential tremor (ET). Sixty five patients had a positive family history. Onset age showed two peaks before 20 years and in the sixth decade. Segregation analysis confirmed an autosomal dominant inheritance. Head tremor occurred mainly in aged women, mental symptoms occurred mainly in subjects with a low onset age and a disabling tremor. An early onset age was not related to paternal or maternal transmission. In one family ET was associated with retinitis pigmentosa and ichthyosis.     

Volume increases in striatum associated with positive symptom reduction in schizophrenia: a preliminary observation

Eleven drug-free patients with a DSM-IV diagnosis of schizophrenia who were in a period of psychotic exacerbation were treated with antipsychotics for 4 weeks. To evaluate treatment-associated changes in the basal ganglia and in psychotic symptomatology, the patients were studied with magnetic resonance imaging and with the Scale for the Assessment of Positive Symptoms. Serial assessments of striatal volumes and psychotic symptoms were performed at baseline and at 4 weeks of treatment; dual assessments of striatal volumes were also performed in 11 untreated normal controls. Patients and controls did not differ in striatal volumes at baseline, but the patients demonstrated a significant posttreatment increase in striatal tissues (caudate-putamen). An increase in left striatum was not associated with drug treatment itself, but with a reduction of positive symptoms.     

Case of acute brainstem and striatal encephalopathy associated with Mycoplasma pneumoniae infection

Acute encephalopathy with bilateral striatal necrosis (EBSN) is a rare reversible neurological disease characterized by an abrupt onset following an acute infectious disease and by severe extra-pyramidal signs associated with striatal lesions. Brainstem involvement is rarely observed in this disease. We report a 10-year-old boy who had EBSN associated with Mycoplasma pneumoniae. He became lethargic after acute bronchitis. A few days later, he showed extra-pyramidal signs, pyramidal signs and overactive urinary bladder symptoms. Cranial T2-weighted and diffusion-weighted magnetic resonance imaging (MRI) demonstrated high-signal intensity in the bilateral striatum and substantia nigra. These symptoms improved soon after the administration of L-dopa in the acute phase. The effects of corticosteroids were not apparent in the acute phase. The serum particle agglutination titers against Mycoplasma pneumoniae determined on admission, the 12th hospital day and 2 months later were 1:2,560, 1:2,560 and 1:320, respectively. Two years later, a mild tic was observed. A mild atrophy was noted in the bilateral basal ganglia, but not in the substantia nigra on cranial MRI. This case is the first reported one with EBSN with the presence of an overactive urinary bladder, which could possibly caused by loss of dopaminergic inhibition.     

Frontal lobe psychopathology: mania, depression, confabulation, catatonia, perseveration, obsessive compulsions, and schizophrenia

The frontal lobes can be subdivided into major functional neuroanatomical domains, which, when injured, surgically destroyed, or reduced in activity or volume, give rise to signature pathological and psychiatric symptomology. A review of case reports and over 50 years of research, including magnetic resonance imaging, positron emission tomography, and single photon emission computed tomography scans, indicates that apathy, "blunted" schizophrenia, major depression, and aphasic-perseverative disturbance of speech and thought are associated with left lateral as well as bilateral frontal (and striatal) abnormalities. Impulsiveness, confabulatory verbosity, grandiosity, increased sexuality, and mania are associated with right frontal (as well as bilateral) disturbances. Gegenhalten, catatonia, and disturbances of "will" are indicative of medial frontal injuries. Disinhibitory states and obsessive-compulsive perseverative abnormalities are more frequently observed with orbital frontal lobe dysfunction, including frontal-striatal disturbances. These associations, however, are not always clear-cut as patients with the same diagnosis may demonstrate different symptoms that may be due to an additional abnormality in a different region of the brain. Moreover, as the frontal subdivisions are richly interconnected, and as frontal lobe abnormalities are not always discrete or well localized, a wide array of seemingly divergent waxing and waning symptoms may be manifest, sometimes simultaneously, including manic depression and what has been referred to as the "frontal lobe personality."     

Cerebrospinal fluid GABA and homocarnosine concentrations in patients with Friedreich's ataxia, Parkinson's disease, and Huntington's chorea

Free and total gamma-aminobutyric acid (GABA) and homocarnosine concentrations were measured in the lumbar cerebrospinal fluid (CSF) of patients with Friedreich's ataxia, Huntington's chorea, and Parkinson's disease (with and without levodopa treatment), and compared with those determined in control subjects. Values found in Friedreich's ataxia or Parkinson's disease were not significantly different from those in controls. Unexpectedly, in Huntington patients, known to have a characteristic decrease in GABA concentrations in specific brain areas, CSF concentrations of total GABA and homocarnosine were significantly higher, whereas free GABA was not different from controls. These findings indicate that the measurement of CSF GABA and homocarnosine in patients with CNS degenerative diseases should be interpreted cautiously.     

Familial idiopathic striato-pallido-dentate calcifications: clinical and brain imaging study in a family

Familial idiopathic basal ganglia calcification (FIBGC) is a rare condition and its pathophysiology has not so far been elucidated. We report the results of a clinical study in two patients of a family affected with FIBGC. Brain imaging with 18-FDG-PET was performed in one. Psychiatric and cognitive troubles were the main clinical symptoms. Basal ganglia calcifications were associated with white matter lesions. The PET study performed in one patient revealed a striatal and a posterior cingulate hypometabolism. Posterior cingulate gyrus is involved in episodic memory processing, and could be involved in episodic memory deficit observed in this patient. These results suggest that a cortical dysfunction could be associated to the disease. The underlying mechanism, that could be a neuronal loss, a cortical deafferentation or an alteration of synaptic transmission, remains to be elucidated.     

Bilateral striatal necrosis, dystonia and optic atrophy in two siblings.

Two siblings developed a neurological disorder in the first decade characterised by generalised dystonia, hypokinesia, and subacute visual loss. CT and serial MRI examinations showed bilateral lesions of the striatum, mainly in the putamen. The classification of these patients is discussed in relation to infantile bilateral striatal necrosis (IBSN), Leigh's disease, and Leber's optic neuropathy. The literature shows a clinical and aetiopathogenetic overlap between these syndromes. In our cases parental consanguinity and the involvement of a single generation suggest a new clinical condition with autosomal recessive transmission.     

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.     

Clinical science

Ognen A. C. Petroff , Fahmeed Hyder , Douglas L. Rothman , and Richard H. Mattson
Yale researchers in pioneering work have been able to study the effects of antiepileptic drugs (AEDs) on the brain chemistry of people with epilepsy in a safe and painless manner by using the principles of magnetic resonance imaging (MRI). Neurons in the human brain make homocarnosine from γ-aminobutyric acid (GABA; the brain's main inhibitory neurotransmitter) and histidine in larger amounts than the neurons of almost all other animals. Three of the newer AEDs, gabapentin (GBP; Neurontin), topiramate (TPM; Topamax), and vigabatrin (Sabril), increase human homocarnosine levels. We measured homocarnosine and GABA levels of 20 patients with complex partial seizures taking GBP and 17 patients taking TPM. Homocarnosine levels were higher in patients with better seizure control than in those whose seizure control was below the middle value (median) for the two groups. No differences were found in the GABA levels between the patients, who showed a better response to GBP or TPM, compared with those who did not. Higher homocarnosine levels (above the median) were associated with better seizure control in the patients taking GBP or TPM; higher brain GABA levels appeared to offer no additional protection. The current results are similar to our previously published findings, which showed higher brain homocarnosine levels in patients with juvenile myoclonic epilepsy with excellent seizure control, taking valproate (Depakote) or lamotrigine (Lamictal), than the levels of patients with more frequent seizures. The data support the hypothesis that increased homocarnosine and GABA levels contribute to the anticonvulsant properties of GBP and TPM, perhaps by limiting the spread of seizures from the areas where seizures start.     

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.     

Clinical features of proven basilar artery occlusion

Our study describes the early symptoms and signs of 85 patients with either basilar artery occlusion or bilateral distal vertebral artery occlusion documented by selective angiography. The most common prodromal symptoms were vertigo, nausea, and headache, which occurred during the 2 weeks before the stroke. Angiographic findings of 49 patients were classified into proximal, middle, and distal basilar artery occlusions. Twenty-two of these patients had additional vertebral artery lesions. A fourth group was composed of 36 patients with bilateral distal vertebral artery occlusion without opacification of the basilar artery through a vertebral artery injection. Onset was sudden in 20 patients; sudden, but preceded by prodromal symptoms in 11 patients; and progressive in 54 patients. Patients with progressive strokes often had bilateral vertebral artery occlusions. Most patients with acute onset had occlusion of the middle and distal basilar artery. An embolic origin of basilar artery occlusion from an arteriosclerotic vertebral artery lesion was assumed to be an important mechanism. An embolus reaching the basilar artery may not necessarily reach the top of the artery, but may also become lodged more proximally.     

Homocarnosine and seizure control in juvenile myoclonic epilepsy and complex partial seizures

OBJECTIVE: To assess the relationship between seizure control and gamma-aminobutyric acid (GABA), homocarnosine, and pyrrolidinone levels in the visual cortex of patients with epilepsy taking valproate or lamotrigine. Previous studies suggested that poor seizure control was associated with low GABA and homocarnosine levels. METHODS: In vivo measurements of GABA, homocarnosine, and pyrrolidinone were made in a 14-cm(3) volume of the occipital cortex using (1)H spectroscopy with a 2.1-Tesla MR spectrometer and an 8-cm surface coil. Twenty-six adults (eight men) taking valproate or lamotrigine were recruited; 12 had complex partial seizures (CPS) and 14 had juvenile myoclonic epilepsy (JME). RESULTS: Median homocarnosine levels were normal for patients with JME and below normal for patients with CPS. Better seizure control was associated with higher homocarnosine levels for both groups. Median GABA was below normal for patients with JME, lower than for patients with CPS. Brain GABA was lowest in patients with JME even when seizure control was excellent. Pyrrolidinone levels were above normal in almost all patients with JME. CONCLUSIONS: Low GABA levels are associated with poor seizure control in patients with CPS, but not in JME. Higher homocarnosine levels are associated with better seizure control in both types of epilepsy.     

Parkinson's disease in Taiwan: an analysis of 215 patients.

215 Chinese Parkinson's disease (PD) patients on levodopa therapy were followed up between 1982 and 1991. The ratio of males to females was 2.4 to 1. The mean durations from onset of the illness to stages I and II of Hoehn and Yahr (mild disability) were 4.0 and 6.5 years, to stage III (moderate) 7.9 years, and to stages IV and V (severe) 9.8 and 11.8 years. The mean duration of illness for living patients was 8.6 years. The mean duration of illness before death for the 46 patients who died was 8.9 years. The mean age at death was 68 years (4.4 years less than the normal life expectancy in Taiwan). The fate of this disease showed that patients with unilateral symptoms initially had a better prognosis than those with bilateral symptoms. The symptoms at onset were unilateral in 70% of the patients, of whom 91% had a spread of symptoms to the opposite side after a mean of 3.4 years. Familial PD occurred in 2.8% of our patients. The occurrence of blood ABO groups was not significantly different between the PD patients and the general population of Taiwan. Our findings differed from those in Western series by having a predominance of males, and a relatively shorter duration of unilateral symptoms before spread to the opposite side. In addition, the duration of illness and the survival time under levodopa treatment were shorter in Taiwanese and Japanese than in Western series.     

HOMOCARNOSINOSIS. 2. A FAMILIAL METABOLIC DISORDER ASSOCIATED WITH SPASTIC PARAPLEGIA, PROGRESSIVE MENTAL DEFICIENCY, and RETINAL PIGMENTATION

Homocarnosine, the brain-specific dipeptide of gamma-aminobutyric acid (GABA) and histidine, was found to be elevated in the CSF, i.e. approximately 20 times the mean control level, in two brothers and one sister. All three were similarly afflicted, i.e. with a progressive spastic paraplegia, progressive mental deterioration and retinal pigmentation. A sister was healthy, and there was no other occurrence of similar symptoms in the family. The clinical symptoms in the affected individuals seem to differ from those in other reported families. The unaffected sister, the father and two maternal aunts exhibited a normal CSF homocarnosine level, whereas the mother, who showed no definite clinical symptoms, showed a markedly elevated CSF homocarnosine level. The explanation for the latter finding remains obscure.     

Striatal Dopamine and Reward Prediction Error Signaling in Unmedicated Schizophrenia Patients

Increased striatal dopamine synthesis capacity has consistently been reported in patients with schizophrenia. However, the mechanism translating this into behavior and symptoms remains unclear. It has been proposed that heightened striatal dopamine may blunt dopaminergic reward prediction error signaling during reinforcement learning. In this study, we investigated striatal dopamine synthesis capacity, reward prediction errors, and their association in unmedicated schizophrenia patients (n = 19) and healthy controls (n = 23). They took part in FDOPA-PET and underwent functional magnetic resonance imaging (fMRI) scanning, where they performed a reversal-learning paradigm. The groups were compared regarding dopamine synthesis capacity (Ki^cer), fMRI neural prediction error signals, and the correlation of both. Patients did not differ from controls with respect to striatal Ki^cer. Taking into account, comorbid alcohol abuse revealed that patients without such abuse showed elevated Ki^cer in the associative striatum, while those with abuse did not differ from controls. Comparing all patients to controls, patients performed worse during reversal learning and displayed reduced prediction error signaling in the ventral striatum. In controls, Ki^cer in the limbic striatum correlated with higher reward prediction error signaling, while there was no significant association in patients. Ki^cer in the associative striatum correlated with higher positive symptoms and blunted reward prediction error signaling was associated with negative symptoms. Our results suggest a dissociation between striatal subregions and symptom domains, with elevated dopamine synthesis capacity in the associative striatum contributing to positive symptoms while blunted prediction error signaling in the ventral striatum related to negative symptoms.     

Visual disturbances representing occipital lobe epilepsy in patients with cerebral calcifications and coeliac disease: a case series

Paroxysmal visual manifestations may represent epileptic seizures arising from the occipital lobe. In coeliac disease (CD) bilateral occipital calcifications and seizure semiology consistent with an occipital origin have been described, primarily in Mediterranean countries. By reporting three adult patients from an Australian outpatient clinic with visual disturbances, occipital cerebral calcifications, and CD, this study seeks to emphasise that CD should be considered even when patients of non-Mediterranean origin present with these symptoms. Seizure types included simple partial, complex-partial, and secondarily generalised seizures. The seizure semiology consisted of visual disturbances such as: blurred vision, loss of focus, seeing coloured dots, and brief stereotyped complex visual hallucinations like seeing unfamiliar faces or scenes. Symptoms of malabsorption were not always present. Neurological examination was unremarkable in two patients, impaired dexterity and mild hemiatrophy on the left was noted in one. Routine electroencephalography was unremarkable. In all cases, computed tomography demonstrated bilateral cortical calcification of the occipital-parietal regions. Magnetic resonance imaging showed no additional lesion. All patients had biopsy confirmed CD. Seizure control improved after treatment with gluten free diet and anticonvulsants. This report illustrates the association between seizures of occipital origin, cerebral calcifications, and CD even in patients not of Mediterranean origin.     

线粒体脑肌病伴有高乳酸血症和卒中样发作综合征的临床及基因突变分析

目的 探讨线粒体脑肌病伴有高乳酸血症和卒中样发作综合征(MELAS)的临床及基因突变特征. 方法 对1例MELAS患者的临床表现、影像学、肌肉病理特点进行分析,并用PCR-RFLP结合基因测序方法进行线粒体基因突变分析. 结果 患者主要临床表现为发作性头痛和呕吐、反复卒中样发作、癫痫、运动不耐受、身材矮小、神经性耳聋、乳酸水平升高等.脑CT见双侧基底节多个钙化灶,MRI见枕叶异常信号,1H-MRS见T2WI异常信号区域有明显的乳酸峰,在T2正常信号区域也有小的乳酸峰.光镜及电镜肌肉病理检查未见明显的线粒体异常,基因检测显示mtDNA A3243G杂合突变. 结论 MELAS的诊断必须结合临床表现、影像学、病理学和基因突变检测等结果进行综合分析,病理学检查阴性不能否定MELAS的诊断,诊断MELAS应常规进行mtDNA突变分析.