A More Homogeneous Phenotype in Parkinson's Disease Related to R1441G Mutation in the LRRK2 Gene.

Parkinson's disease (PD) is characterized by a great clinical heterogeneity. Nevertheless, the biological drivers of this heterogeneity have not been completely elucidated and are likely to be complex, arising from interactions between genetic, epigenetic, and environmental factors. Despite this heterogeneity, the clinical patterns of monogenic forms of PD have usually maintained a good clinical correlation with each mutation once a sufficient number of patients have been studied. Mutations in LRRK2 are the most commonly known genetic cause of autosomal dominant PD known to date. Furthermore, recent genome-wide association studies have revealed variations in LRRK2 as significant risk factors also for the development of sporadic PD. The LRRK2-R1441G mutation is especially frequent in the population of Basque ascent based on a possible founder effect, being responsible for almost 50% of cases of familial PD in our region, with a high penetrance. Curiously, Lewy bodies, considered the neuropathological hallmark of PD, are absent in a significant subset of LRRK2-PD cases. Indeed, these cases appear to be associated with a less aggressive primarily pure motor phenotype. The aim of our research is to examine the clinical phenotype of R1441G-PD patients, more homogeneous when we compare it with sporadic PD patients or with patients carrying other LRRK2 mutations, and reflect on the value of the observed correlation in the genetic forms of PD. The clinical heterogeneity of PD leads us to think that there may be as many different diseases as the number of people affected. Undoubtedly, genetics constitutes a relevant key player, as it may significantly influence the phenotype, with differences according to the mutation within the same gene, and not only in familial PD but also in sporadic forms. Thus, extending our knowledge regarding genetic forms of PD implies an expansion of knowledge regarding sporadic forms, and this may be relevant due to the future therapeutic implications of all forms of PD.

The goblet sign in the amnestic syndrome of the subcallosal artery infarct.

We here describe an acute-onset amnesic syndrome with evidence of an embolic infarction in the distribution of the subcallosal artery, a proximal branch of the anterior communicating artery. The infarction involved the corpus callosum genu and both fornices, giving a peculiar image on MRI that resembled a goblet. Although infrequent, the subcallosal artery infarction should be considered in the differential diagnosis of patients with an acute amnestic syndrome. We propose "the goblet sign" for the peculiar diffusion-weighted MRI image of the brain in this syndrome.

Alteraciones reversibles en los núcleos dentados y atrofia cerebral de rápida instauración debido a neurotoxicidad por litio / Reversible alterations in the dentate nuclei and rapid-onset cerebral atrophy due to neurotoxicity caused by lithium

Introducción. El tratamiento con litio puede ocasionar diversos efectos adversos neurológicos, incluso con niveles terapéuticos. Caso clínico. Mujer de 49 años, con trastorno bipolar y depresión, en tratamiento con litio, antidepresivos y antipsicóticos, que ingresó por un cuadro de alucinaciones visuales con una litemia elevada de 2,1 mEq/L (rango terapéutico: 0,6-1,2 mEq/L). Progresó a una encefalopatía grave que requirió asistencia respiratoria en la unidad de cuidados intensivos. La resonancia magnética cerebral inicial mostró una hiperintensidad simétrica bilateral reversible en los núcleos dentados en las secuencias T2 y T2-FLAIR. A lo largo de los meses posteriores desarrolló de forma progresiva un síndrome pancerebeloso con evidencia de una marcada pérdida de volumen bilateral en el cerebelo, sobre todo a expensas del vermis, que se acompañó clínicamente de un síndrome cerebeloso permanente e invalidante. Conclusiones. Aunque el tratamiento con litio ocasiona efectos adversos neurológicos variados, éstos suelen ser reversibles. Puede dar lugar a secuelas permanentes e incapacitantes, como la paciente descrita, con una atrofia cerebelosa marcada y progresiva, acompañada de secuelas permanentes en forma de síndrome cerebeloso invalidante. La neurotoxicidad cerebelosa del litio debe considerarse en el amplio diagnóstico diferencial que representa la ataxia cerebelosa del adulto (AU)

Introduction. Treatment with lithium can cause several neurological side effects, even at therapeutic levels. Case report. We report the case of a 49-year-old woman, with bipolar disorder and depression, undergoing treatment with lithium, antidepressants and antipsychotics, who was admitted to hospital due to a clinical picture of visual hallucinations with an elevated lithaemia of 2.1 mEq/L (therapeutic range: 0.6-1.2 mEq/L). The patient developed a severe encephalopathy that required the use of assisted ventilation in the intensive care unit. Initial magnetic resonance imaging showed a reversible bilateral symmetrical hyperintensity in the dentate nuclei in T2 and T2-FLAIR sequences. Over the following months she gradually developed a pancerebellar syndrome with evidence of a marked loss of bilateral volume in the cerebellum, above all at the expense of the vermis, which was accompanied by a permanent and disabling cerebellar syndrome. Conclusions. Although treatment with lithium can cause a variety of neurological side effects, they are usually reversible. However, they occasionally give rise to permanent and disabling sequelae, as in the case of the patient reported here, with a marked and progressive cerebellar atrophy, accompanied by permanent sequelae in the form of a disabling cerebellar syndrome. The cerebellar neurotoxicity of lithium must be taken into account in the broad differential diagnosis of cerebellar ataxia in adults (AU)

Faciolingual Hemiparesis with Mild Limb Weakness of Cortical Origin.

The clinical combination of unilateral facial and hypoglossal palsy with upper limb weakness is known as the capsular genu syndrome and responds most often to an ischemic infarct in the internal capsule. We here describe a patient with this peculiar combination, in whom the responsible lesion was located in the contralateral prefrontal cortex, involving the corresponding areas of the Penfield's homunculus. Contralateral cortical frontal lesions should be considered in patients with facial and hypoglossal palsy with upper limb weakness.