• Alcohol
• Alcohol metabolism
• Alcoholism
• Neurological disorders
• Neurotransmitter

• Alcohol intoxication
• Alcohol withdrawal
• Alcohol-related dementia
• Cerebellar degeneration
• Hepatic encephalopathy
• Korsakoff syndrome
• Peripheral neuropathy
• Wernicke encephalopathy

• Humans
• Hepatic Encephalopathy/etiology
• Hepatic Encephalopathy/diagnosis
• Alcoholism/complications
• Diagnosis, Differential
• Peripheral Nervous System Diseases/etiology
• Alcohol Drinking/adverse effects
• Dementia/etiology
• Korsakoff Syndrome/etiology
• Korsakoff Syndrome/diagnosis
• Alcoholic Korsakoff Syndrome/etiology
• Alcoholic Korsakoff Syndrome/diagnosis
• Alcoholic Neuropathy/etiology
• Alcoholic Neuropathy/diagnosis

• Alcohol use disorder
• Biotyping
• Genetic association analysis
• Machine learning
• Nicotine use disorder
• Resting-state functional magnetic resonance imaging (MRI)

• Humans
• Tobacco Use Disorder
• Alcoholism/diagnostic imaging
• Magnetic Resonance Imaging
• Anxiety Disorders
• Machine Learning

• K02 DA043063 NIDA NIH HHS
• R01 DA051922 NIDA NIH HHS

• COVID-19
• Korsakoff’s syndrome
• Wernicke’s encephalopathy
• alcoholic cerebellar degeneration
• cerebellar atrophy
• cerebellar cognitive affective syndrome
• cerebellar disfunction
• neuropsychology
• nutritional cerebellar degeneration
• thiamine deficiency

• Alcohol
• Binge drinking
• C-Fos
• IntelliCage
• Light-sheet microscopy

• ACE, Angiotensin-Converting-Enzyme
• ALD, Alcohol related Liver Disease
• AUD, Alcohol Use Disorder
• GAVE, Gastric Antral Vascular Ectasia
• GERD, Gastro-Esophageal Reflux Disease
• HCC, Hepatocellular Carcinoma
• HIV, Human Immunodeficiency Virus
• IARC, International Agency for Research on Cancer
• IL, Interleukin
• NERD, Non-Erosive Reflux Disease
• PPI, Proton Pump Inhibitors
• TNF, Tumour Necrosis Factor
• UGI, Upper Gastrointestinal
• WHO, World Health Organization
• alcohol use disorder
• alcohol withdrawal syndrome
• alcoholic cardiomyopathy
• alcoholic liver disease
• alcoholic myopathy

• Alcohol Use Disorder
• Ataxia
• Cerebellum
• Functional Connectivity
• Resting-state fMRI

• Alcohol Drinking
• Alcoholism
• Ataxia
• Brain
• Cerebellum/diagnostic imaging
• Humans
• Magnetic Resonance Imaging/methods
• Neural Pathways

• R01 AA010723 NIAAA NIH HHS
• R37 AA010723 NIAAA NIH HHS

MRI shows the three archetypal patterns of CNS volume loss underlying progressive ataxias in vivo, namely spinal atrophy (SA), cortical cerebellar atrophy (CCA) and olivopontocerebellar atrophy (OPCA). The MRI-based CNS atrophy pattern was reviewed in 128 progressive ataxias. A CNS atrophy pattern was identified in 91 conditions: SA in Friedreich’s ataxia, CCA in 5 acquired and 72 (24 dominant, 47 recessive,1 X-linked) inherited ataxias, OPCA in Multi-System Atrophy and 12 (9 dominant, 2 recessive,1 X-linked) inherited ataxias. The MRI-based CNS atrophy pattern may be useful for genetic assessment, identification of shared cellular targets, repurposing therapies or the enlargement of drug indications in progressive ataxias.

Although Krüppel-associated box domain-containing zinc-finger proteins (K-ZNFs) may be associated with sophisticated gene regulation in higher organisms, the physiological functions of most K-ZNFs remain unknown. The Zfp212 protein was highly conserved in mammals and abundant in the brain; it was mainly expressed in the cerebellum (Cb). Zfp212 (mouse homolog of human ZNF212) knockout (Zfp212-KO) mice showed a reduction in survival rate compared to wild-type mice after 20 months of age. GABAergic Purkinje cell degeneration in the Cb and aberrant locomotion were observed in adult Zfp212-KO mice. To identify genes related to the ataxia-like phenotype of Zfp212-KO mice, 39 ataxia-associated genes in the Cb were monitored. Substantial alterations in the expression of ataxin 10, protein phosphatase 2 regulatory subunit beta, protein kinase C gamma, and phospholipase D3 (Pld3) were observed. Among them, Pld3 alone was tightly regulated by Flag-tagged ZNF212 overexpression or Zfp212 knockdown in the HT22 cell line. The Cyclic Amplification and Selection of Targets assay identified the TATTTC sequence as a recognition motif of ZNF212, and these motifs occurred in both human and mouse PLD3 gene promoters. Adeno-associated virus-mediated introduction of human ZNF212 into the Cb of 3-week-old Zfp212-KO mice prevented Purkinje cell death and motor behavioral deficits. We confirmed the reduction of Zfp212 and Pld3 in the Cb of an alcohol-induced cerebellar degeneration mouse model, suggesting that the ZNF212–PLD3 relationship is important for Purkinje cell survival.

The association of movement disorders with structural or functional hepatic disease occurs in three principal scenarios: (1) combined involvement of both organ systems from a single disease entity, (2) nervous system dysfunction resulting from exposure to toxic compounds in the setting of defective hepatic clearance, or (3) hepatic and/or neurological injury secondary to exposure to exogenous drugs or toxins. An important early step in the workup of any patient with combined movement disorders and liver disease is the exclusion of Wilson's disease. Diagnostic delay remains common for this treatable disorder, and this has major implications for patient outcomes. Thereafter, a structured approach integrating variables such as age of onset, tempo of progression, nature and severity of liver involvement, movement disorder phenomenology, exposure to drugs/toxins and laboratory/neuroimaging findings is key to ensuring timely diagnosis and disease‐specific therapy. Herein, we provide an overview of disorders which may manifest with a combination of movement disorders and liver disease, structured under the three headings as detailed above. In each section, the most common disorders are discussed, along with important clinical pearls, suggested diagnostic workup, differential diagnoses and where appropriate, treatment considerations.

• liver diseases
• movement disorders

• Epigenetics
• addiction
• aging
• alcoholism
• ataxia
• dementia
• inflammation
• stress

• alcohol consumption
• brain atrophy
• japanese population
• neuroimaging
• voxel-based morphometry

• Adult
• Aged
• Alcohol Drinking
• Brain/diagnostic imaging
• Gray Matter/diagnostic imaging
• Humans
• Japan
• Magnetic Resonance Imaging
• Male
• Middle Aged

• R01 HL068200 NHLBI NIH HHS

Cerebellar ataxias (CAs) are neurological diseases characterized by loss of muscle coordination that is a result of damage and inflammation to the cerebellum. Despite considerable efforts in basic and clinical research, most CAs are currently incurable. In this study, we evaluated the therapeutic potential of human mesenchymal stem cells (hMSCs) against CAs associated with neuroinflammation. We observed that hMSC treatment significantly inhibited the symptoms of ataxia in lipopolysaccharide (LPS)-induced inflammatory CA (ICA) mice, which were recently reported as a potential animal model of ICA, through the anti-inflammatory effect of hMSC-derived TNFα-stimulated gene-6 (TSG-6), the protection of Purkinje cells by inhibition of apoptosis, and the modulatory effect for microglial M2 polarization. Thus, our results suggest that hMSC treatment may be an effective therapeutic approach for preventing or improving ataxia symptoms.

• cerebellar ataxia
• lipopolysaccharide
• mesenchymal stem cell
• microglia
• neuroinflammation

Most cerebellar ataxias (CAs) are incurable neurological disorders, resulting in a lack of voluntary control by inflamed or damaged cerebellum. Although CA can be either directly or indirectly related to cerebellar inflammation, there is no suitable animal model of CA with neuroinflammation. In this study, we evaluated the utility of an intracerebellar injection of lipopolysaccharide (LPS) to generate an animal model of inflammatory CA. We observed that LPS administration induced the expression of pro-inflammatory molecules following activation of glial cells. In addition, the administration of LPS resulted in apoptotic Purkinje cell death and induced abnormal locomotor activities, such as impaired motor coordination and abnormal hindlimb clasping posture. Our results suggest that intracerebellar LPS administration in experimental animals may be useful for studying the inflammatory component of CA.

• Alcohol
• immune system
• multiple sclerosis

• Alcohol
• Ataxia
• Multiple system atrophy
• Parkinsonism
• Smoking

• Age of Onset
• Aged
• Aged, 80 and over
• Alcoholism/epidemiology
• Ataxia/epidemiology
• Comorbidity
• Female
• Humans
• Male
• Middle Aged
• Multiple System Atrophy/epidemiology
• Multiple System Atrophy/mortality
• Smoking/epidemiology

• R01 FD004789 FDA HHS
• R01 NS092625 NINDS NIH HHS
• U54 NS065736 NINDS NIH HHS
• K23 NS075141 NINDS NIH HHS
• UL1 TR000135 NCATS NIH HHS
• P01 NS044233 NINDS NIH HHS

• Ataxia
• Cerebellar degeneration
• Cerebellum
• Epilepsy
• Phenytoin

• Aging
• Cerebellum:Histone acetylation
• Chronic ethanol
• Histone deacetylases
• Purkinje neuron

• Alcoholismo
• Complicaciones neurológicas
• Encefalopatía hepática
• Excessive alcohol consumption
• Hepatic encephalopathy
• Neurological complications

Cerebellar ataxia with sensory ganglionopathy is a rare neurological combination that can occur in some hereditary ataxias including mitochondrial diseases and in gluten sensitivity. Individually each condition can be a classic paraneoplastic neurological syndrome. We report a patient with this combination who was diagnosed with light-chain myeloma ten years after initial presentation.

A 65-year-old Caucasian lady was referred to our Ataxia Clinic because of a 6-year history of progressive unsteadiness and a 2-year history of slurred speech. Past medical history included arterial hypertension. The patient was a non-smoker was not consuming alcohol excessively. There was no family history of ataxia.

Neurological examination revealed prominent gaze-evoked nystagmus, heel to shin ataxia, gait ataxia, reduced reflexes and loss of vibration sensation in the legs.

Cerebellar ataxia was confirmed using magnetic resonance spectroscopy of the cerebellum and sensory ganglionopathy using neurophysiological assessments including blink reflex study. A muscle biopsy that was arranged to explore the possibility of mitochondrial disease revealed amyloidosis. Urinalysis confirmed the presence of light chains. A bone marrow biopsy confirmed the diagnosis of light chain multiple myeloma.

Whilst it could be argued that this could simply be a coincidence, the rarity of these conditions and the absence of an alternative aetiology for the neurological dysfunction argue in favour of a paraneoplastic phenomenon.

The online version of this article (doi:10.1186/s40673-016-0060-4) contains supplementary material, which is available to authorized users.

• Amyloid
• Ataxia
• Cerebellar
• Myeloma
• Paraneoplastic
• Sensory ganglionopathy