Paramagnetic Substance Deposition Research Articles

Hypermanganesemia with Dystonia Type 2: A Rare Entity. (P12-11.001)

<h3>Objective:</h3> NA <h3>Background:</h3> Hypermanganesemia with dystonia type 2 is an established, rare autosomal recessive partially reversible neurodegenerative condition characterised by mutations in the SLC39A14 gene. Manganese deposition in such cases has a special predilection for the basal ganglia structures leading to dystonia and parkinsonian features. We report such a case of hypermanganesemia in a 1 year old child presenting with extrapyramidal features. <h3>Design/Methods:</h3> NA <h3>Results:</h3> A 1 year old female child presented with regression of developmental milestones for the past 2 months, losing the ability to stand or even sit without support—skills that she had previously acquired at an appropriate time. This was associated with dystonic posturing of her neck and limbs for the last 1 month. Cognitive skills were normal as per her age without any history of convulsions or other systemic features. Her birth and family history were unremarkable. Her neurological examination was remarkable only for generalised dystonia of her limbs, neck and trunk. Magnetic resonance imaging was suggestive of paramagnetic substance deposition in bilateral basal ganglia and dentate nucleus. Normal routine blood parameters were followed by extensive investigations to rule out Wilson’s disease, NBIA and other autoimmune pathologies. Her blood manganese levels were significantly elevated and her genetic sequencing revealed compound heterozygous mutations of the SLC39A14 gene at exons 7 and 8. She was started on chelation therapy with Penicillamine and oral iron. Dystonia resolved significantly by the end of 6 months of therapy with marked improvement in her motor developmental milestones. <h3>Conclusions:</h3> Hypermanganesemia with dystonia type 2 (HMNDYT2) is a rare genetic disorder characterised by neuronal manganese deposition without other systemic features. This case highlights the importance of recognising this potentially rare treatable condition and with adequate chelation therapy at the right time, near total restoration of motor symptomatology is possible. <b>Disclosure:</b> Dr. Bhattacharya has nothing to disclose. Dr. Chintha has nothing to disclose. Dr. Biswas has nothing to disclose. Dr. Das has nothing to disclose. Dr. Chakraborty has nothing to disclose. Dr. Mukherjee has nothing to disclose.

Acute hemichorea with T1 ischemic hyperintensity associated with steno‐occlusive middle cerebral artery dissection

AbstractAcute hemichorea with accompanying T1 hyperintensity on magnetic resonance imaging has never been reported in steno‐occlusive middle cerebral artery (MCA) dissection. This characteristic radiological finding which differs from known ischemic changes has been attributed to incomplete infarction with selective neuronal loss. Arguments have also shuttled between gemistocytic astrocyte accumulation, tissue calcification, and paramagnetic substance deposition. We report an unusual case of acute hemichorea caused by proximal MCA dissection with characteristic imaging appearance of delayed ischemic hyperintensity.

Comparison of brain magnetic resonance imaging findings before and after liver transplantation

Aim: The purpose was to compare the brain Magnetic Resonance Imaging (MRI) findings of the liver transplant recipients who had a neurological symptom, before and after liver transplantation. Material and Methods: Patients were evaluated in the terms of age, gender, etiology of chronic liver disease and the clinical symptoms. The brain MRI findings before and after liver transplantation were compared. Results: Thirty liver transplant patients with brain MRIs before and after liver transplantation were included. Hyper intensities on T1 weighted images which is compatible with manganese deposition in the basal ganglia was found from the first brain MRI of 18 patients. In thirteen of them the deposition was disappeared or decreased but in five of them the deposition persisted after transplantation. Hyper intensities on T2 weighted images which is compatible with copper deposition in the basal ganglia of four patients with Wilson’s disease persisted after transplantation. Five patients who had normal brain MRI findings before transplantation had posterior reversible encephalopathy syndrome (PRES) after the transplantation. One patient had focal cerebritis, three patients had acute infarct and one patient had intraparenchymal hemorrhage after transplantation. Conclusion: Most of the neurological symptoms during chronic liver disease are associated with the deposition of paramagnetic substances. After transplantation there could be regression in manganese deposition but the copper deposition stayed the same. Post-transplant PRES, central nervous system infections, infarct, and hemorrhage were not rare. Pre and post-transplant patients with neurological symptoms should be evaluated with brain MRI for rapid diagnosis and proper management.

X-linked Parkinsonism with Intellectual Disability caused by novel mutations and somatic mosaicism in RAB39B gene

BackgroundRAB39B pathogenic variants cause X-linked Parkinsonism associated with Intellectual Disability, known as Waisman syndrome, a very rare disorder that has been mainly identified through exome sequencing in large Parkinson's disease cohorts.In this study we searched for pathogenic variants in RAB39B in two Italian families affected by X-linked early-onset Parkinsonism and Intellectual Disability. MethodsThree patients received neurological evaluation and underwent RAB39B sequencing. ResultsTwo novel RAB39B frameshift variants were found to result in the absence of RAB39B protein (family 1: c.137dupT; family 2: c.371delA). Patients showed unilateral rest tremor and bradykinesia; one of them also displayed an early-onset postural tremor. Paramagnetic substance deposition in the substantia nigra, globus pallidi, red nucleus, putamen and pulvinar was assessed by brain imaging. Two patients also showed moderate calcification of globus pallidi. ConclusionIn this study we highlight the evidence that X-linked early-onset Parkinsonism associated with Intellectual Disability occurs as a pattern of clinical and neuroimaging features attributable to RAB39B pathogenic variants.

Alterations in the basal ganglia in patients with brain tumours may be due to excessive iron deposition.

The accumulation of iron in the brain is a common physiological process. However, alterations in the deposition of iron or other paramagnetic substances are associated with various diseases. In the present study, the deposition of paramagnetic substances in patients with brain tumours was evaluated using T2 relaxometry. A total of 23 patients with untreated tumours or with recurrent tumours following treatment, together with a group of 19 age-matched healthy controls, were examined using T2 relaxometry at 3T. The relaxation times in the basal ganglia, thalamus and white matter were evaluated. Significantly lower T2 relaxation times were identified in the basal ganglia and thalamus of the patients with tumours, as compared with those of the controls (P<0.05). No statistically significant difference was identified between patients with untreated or recurrent brain tumours. The reduction in T2 relaxation times in the brain tumour patients was possibly caused by the accumulation of iron, since iron homeostasis is known to be altered in patients with tumours. We propose that increased iron deposition is a consequence of a higher risk of oxidative stress caused by an increased iron concentration in the plasma or cerebrospinal fluid.

Ischemic hyperintensities on T1-weighted magnetic resonance imaging of patients with stroke: New insights from susceptibility weighted imaging

Hyperintensities on T1-weighted magnetic resonance imaging (MRI) in the setting of brain ischemia are usually considered hemorrhagic transformations. Such changes can also be seen due to "incomplete infarction" with selective neuronal loss. Arguments regarding the cause of these T1 hyperintensities have shuttled between gemistocytic astrocyte accumulation, tissue calcification and paramagnetic substance deposition. Susceptibility weighted imaging (SWI), a sensitive modality for detecting paramagnetic agents and blood products, has never been used to resolve this issue. The study was aimed to evaluate the SWI signal changes of T1 hyperintense lesion in stroke patients and understand its usefulness in differentiating a hemorrhagic infarct and an incomplete infarct. All the seven patients with infarct, having hyperintensities on T1 weighted MR imaging seen over the last one year were subjected to SWI. In none of the patients SWI failed to show any blooming. By doing SWI for T1-weighted hyperintensities, we can differentiate hemorrhagic infarct and a non-hemorrhagic "incomplete infarct". This differentiation will immensely help in planning management strategy and prognostication.

Signal changes in cortical laminar necrosis—evidence from susceptibility-weighted magnetic resonance imaging

Two types of infarcts can be identified depending on the circumstances leading to its generation-infarcts with pannecrosis and infarcts with selective neuronal loss. Cortical laminar necrosis (CLN) can occur due to various etiologies of which infarctions and hypoxia are the commonest. Infarction results in pannecrosis whereas hypoxia and incomplete infarction result in selective neuronal loss with the presence of viable cells, glial proliferations, and deposition of paramagnetic substances. We investigated patients with CLN with susceptibility-weighted imaging (SWI), a technique highly sensitive to even traces of paramagnetic agents or hemorrhagic components. We retrospectively reviewed medical records of patients diagnosed with CLN as per standard criterion. Demographic characteristics and etiologies were recorded. Findings in magnetic resonance images including SWI were analyzed. We identified 11 patients with CLN, six males and five females with age range of 4-64 years. Etiologies included hypoxia in two patients and infarction in the nine patients. SWI detected diffuse linear hypointensities along the gyral margins in CLN due to hypoxic ischemic encephalopathy. Linear dot like hypointensities were identified in one patient with infarction. CLN due to hypoxic ischemic encephalopathy display linear gyral hypointensities and basal ganglia hypointensities that are identifiable in SWI and may represent mineralization. This might be related to iron transport across the surviving neurons from basal ganglia to the cortex, which is not possible in complete infarction. SWI may be helpful in understanding the pathophysiological aspects of CLN due to complete infarction and hypoxia.

Magnetic Resonance Imaging of Brain in Patients with Cirrhotic and Non-Cirrhotic Portal Hypertension

Hyperintense signals in the basal ganglia, namely the globus pallidus, have been reported on magnetic resonance imaging (MRI) in 70-100% of patients with cirrhosis of the liver. Deposition of paramagnetic substances, particularly manganese (Mn), has been reported to be responsible for these hyperintense signals. They are found in cirrhotics with or without overt/subclinical hepatic encephalopathy. Deposition of Mn has been attributed to hepatocellular failure and/or portosystemic shunting. Reports of MRI brain findings in patients with extra hepatic portal venous obstruction (EHPVO) and non-cirrhotic portal fibrosis (NCPF) are scanty in the literature. The purpose was to determine the basal ganglia changes on MRI in patients with EHPVO and NCPF and to compare it with patients with cirrhosis of the liver. A total of 27 patients (EHPVO = 10, mean age 28.4 +/- 19.0 years, NCPF = 7, mean age 37.1 +/- 10.4 years, cirrhosis = 10, mean age 47.0 +/- 19.6 years) was studied prospectively from January to December 2001. MRI of the brain was done with a standard spin echo axial T1- and fast spin echo T2-weighted scan obtained on a 1.5-T MRI unit. Two radiologists in a blinded fashion graded the signal intensity of basal ganglia on T1-weighted (T1 W) sequences by comparing it with the adjacent unaffected grey matter. None of the patients with EHPVO or NCPF had any past history of hepatic decompensation and/or overt encephalopathy. Seven (70%) of the cirrhotics had a past history of overt encephalopathy. None of the patients with EHPVO showed any hyperintensity of basal ganglia on T1-weighted MRI images. Hyperintense globus pallidus was seen in four (57%) and eight (80%) patients with NCPF and cirrhosis, respectively. Hyperintense globus pallidus on MRI is common in patients liver cirrhosis and also occurs in patients with NCPF. Patients with EHPVO do not have hyperintense globus pallidus on T1-weighted MRI images.

Extrahepatic portal vein obstruction with parkinsonism and symmetric hyperintense basal ganglia on T1 weighted MRI

Abnormal high signal in the globus pallidus on T1 weighted magnetic resonance imaging (MRI) of the brain has been well described in patients with chronic liver disease. It may be related to liver dysfunction or portal-systemic shunting. We report a case of extra hepatic portal vein obstruction with portal hypertension and esophageal varices that presented with extra pyramidal features. T1 weighted MRI brain scans showed increased symmetrical signal intensities in the basal ganglia. Normal hepatic function in this patient emphasizes the role of portal- systemic communications in the development of these hyperintensities, which may be due to deposition of paramagnetic substances like manganese in the basal ganglia.

High signal in the adenohypophysis on T1-weighted images presumably due to manganese deposits in patients on long-term parenteral nutrition.

Hypermanganesaemia is reported in patients on long-term parenteral nutrition. Deposition of manganese, giving high signal on T1-weighted images, may involve the basal ganglia. MRI in nine patients (mean age 51 years, range 31-75 years) on long-term parenteral nutrition (mean duration 30 months, range 6-126 months), demonstrated high signal in the anterior pituitary gland on T1-weighted sagittal and coronal images. The gland appeared normal on T2-weighted images. Signal intensity in the basal ganglia on T1-weighted images was increased in all patients. Endocrine assessment showed no significant abnormality. Neurological examination showed a mild parkinsonian movement disorder in one patient. Hypermanganaesemia was present in all nine (1.3-2.8 micromol/l, mean 1.87 micromol/l). The high signal in the anterior pituitary gland was probably related to deposition of paramagnetic substances, especially manganese.

Bright basal ganglia in T1-weighted magnetic resonance images are frequent in patients with portal vein thrombosis without liver cirrhosis and not suggestive of hepatic encephalopathy

Background/Aims: Deposition of paramagnetic substances in basal ganglia, resulting in increased signals in T1-weighted magnetic resonance images (bright basal ganglia), is frequently seen in liver cirhrosis. The present study describes the prevalence of bright basal ganglia and its clinical significance in patients with long-standing portal vein thrombosis in the absence of liver cirrhosis. Methods: Six patients with angiographically proven complete portal vein thrombosis and cavernomatous transformation without signs of acute or chronic liver disease were studied by magnetic resonance imaging of the brain, neuropsychiatric evaluation, psychometric tests, electroencephalography, and determination of arterial ammonia levels and of serum manganese concentrations from peripheral venous blood. Results: Five out of six patients demonstrated increased signal intensity in the basal ganglia. Overt portal-systemic encephalopathy was not noted prior to or at the time of evaluation. Normal EEG results were recorded in all patients. Only one of the six patients had pathological results in at least two out of four psychometric tests. This latter patient had had a large right-sided brain infarction. Arterial ammonia concentrations were normal in four of the six patients; one patient with increased ammonia levels had concomitant renal insufficiency with azotemia. The other four patients had no relevant concomitant diseases. Serum manganese levels were non-significantly increased compared with control group ( p=0.06), but they were significantly correlated to basal ganglia signal intensity (R=0.88; p=0.02). Conclusions: Our results demonstrate that bright basal ganglia primarily represent shunt-induced alterations. They are not directly associated with disturbed liver function nor with portal-systemic encephalopathy.