P: 61 Attenuation of Neurological Symptoms of Type C Hepatic Encephalopathy by Selective Ablation of Neuronal FXR Expression

Hepatic encephalopathy (HE) is a significant complication of both acute and chronic liver disease, causing much morbidity and mortality. It is a complex neuropsychological condition, associated with hyperammonaemia and systemic inflammation, with a wide spectrum of symptoms. The West Haven criteria describe grades of severity from 0 (subclinical) and I (changes in awareness, mood, attention, cognition, and sleep pattern) through to IV (coma). It is further classified by the underlying aetiology: type A, due to acute liver failure; type B, secondary to portosystemic shunting; and type C, occurring in chronic liver disease in association with precipitating factors including infections, gastrointestinal bleeding, and electrolyte disorders, particularly hyponatraemia. There is no definitive test or set of diagnostic criteria to establish a diagnosis of HE, which remains primarily a clinical diagnosis of exclusion in patients with a history or clinical evidence of liver disease. Management depends on the type of HE, but for type C (the commonest type) typically includes lactulose and rifaximin. Patients with cirrhosis with ongoing overt HE despite optimal medical management have a dismal outlook and should be considered promptly for liver transplantation.

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Niemann-Pick Type C Disease - Report on Results from the Niemann-Pick Type C Patient and Healthcare Professional Survey

European Neurological Review ◽

10.17925/enr.2011.06.01.12 ◽

2011 ◽

Vol 6 (1) ◽

pp. 12

Author(s):

Hans H Klünemann ◽

J Edmond Wraith ◽

Frits A Wijburg ◽

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...

Keyword(s):

Healthcare Professional ◽

Specific Treatment ◽

The Body ◽

Neurological Symptoms ◽

Diagnostic Process ◽

Abnormal Accumulation ◽

Recent Developments ◽

Type C ◽

Niemann Pick ◽

Disease Specific

Niemann-Pick type C disease (NPC) is a rare and progressive genetic condition that is associated with an abnormal accumulation of lysosomal lipids in the body, which manifests as a variety of neurological symptoms that range greatly in severity. Management focuses largely on treating symptoms, but recent developments have led to disease-specific therapy that can slow or stabilise the progression of neurological symptoms in some patients. The Niemann-Pick type C Patient and Healthcare Professional Survey conducted interviews with parents and carers of patients with NPC and with healthcare professionals to identify areas of NPC diagnosis, management and support that need improvement. Specifically, an emphasis was placed on increased awareness of the disease and disease symptoms with enhanced communication between doctors, their colleagues and parents of patients in order to facilitate the diagnostic process and the hope for earlier diagnoses, thereby enabling access to disease-specific treatment. The survey identified a need among families of patients with NPC for more support from doctors in the provision of information about the disease and about locally based social and psychological support, and for support from healthcare organisations that should coordinate all the available services. Such co-ordination could ensure that consistent support is provided for all aspects of patient care and for patients’ families and carers.

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Imatinib therapy blocks cerebellar apoptosis and improves neurological symptoms in a mouse model of Niemann‐Pick type C disease

The FASEB Journal ◽

10.1096/fj.07-102715 ◽

2008 ◽

Vol 22 (10) ◽

pp. 3617-3627 ◽

Cited By ~ 61

Author(s):

Alejandra R. Alvarez ◽

Andres Klein ◽

Juan Castro ◽

Gonzalo I. Cancino ◽

Julio Amigo ◽

...

Keyword(s):

Mouse Model ◽

Neurological Symptoms ◽

Imatinib Therapy ◽

Type C ◽

Niemann Pick

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Clinical management of type C hepatic encephalopathy

United European Gastroenterology Journal ◽

10.1177/2050640620909675 ◽

2020 ◽

Vol 8 (5) ◽

pp. 536-543 ◽

Cited By ~ 1

Author(s):

Lorenzo Ridola ◽

Oliviero Riggio ◽

Stefania Gioia ◽

Jessica Faccioli ◽

Silvia Nardelli

Keyword(s):

Hepatic Encephalopathy ◽

Time Course ◽

Standard Of Care ◽

Minimal Hepatic Encephalopathy ◽

Secondary Prophylaxis ◽

Complex Spectrum ◽

Diagnostic Strategies ◽

Clinical Scales ◽

Overt Hepatic Encephalopathy ◽

Type C

Type-C hepatic encephalopathy is a complex neurological syndrome, characteristic of patients with liver disease, causing a wide and complex spectrum of nonspecific neurological and psychiatric manifestations, ranging from a subclinical entity, minimal hepatic encephalopathy, to a deep form in which a complete alteration of consciousness can be observed: overt hepatic encephalopathy. Overt hepatic encephalopathy occurs in 30–40% of patients. According to the time course, hepatic encephalopathy is subdivided into episodic, recurrent and persistent. Diagnostic strategies range from simple clinical scales to more complex psychometric and neurophysiological tools. Therapeutic options may vary between episodic hepatic encephalopathy, in which it is important to define and treat the precipitating factor and hepatic encephalopathy and secondary prophylaxis, where the standard of care is non-absorbable disaccharides and rifaximin. Grey areas and future needs remain the therapeutic approach to minimal hepatic encephalopathy and issues in the design of therapeutic studies for hepatic encephalopathy.

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Charcoal-based hemodiabsorption liver support for episodic type C hepatic encephalopathy

The American Journal of Gastroenterology ◽

10.1111/j.1572-0241.2003.08768.x ◽

2003 ◽

Vol 98 (12) ◽

pp. 2763-2770 ◽

Cited By ~ 4

Author(s):

Kevin Hill ◽

Ke-Qin Hu ◽

Alfred Cottrell ◽

Sigmund Teichman ◽

Donald J. Hillebrand

Keyword(s):

Hepatic Encephalopathy ◽

Liver Support ◽

Type C

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Surgical Management of Chiari Malformations: Preliminary Results of Surgery According to the Mechanisms of Ptosis of the Brain Stem and Cerebellum

Journal of Neurological Surgery Part B Skull Base ◽

10.1055/s-0039-1697977 ◽

2019 ◽

Cited By ~ 1

Author(s):

Misao Nishikawa ◽

Paolo A. Bolognese ◽

Roger W. Kula ◽

Hiromichi Ikuno ◽

Toshihiro Takami ◽

...

Keyword(s):

Brain Stem ◽

Chiari Malformation ◽

Foramen Magnum ◽

Neurological Symptoms ◽

Bone Size ◽

Occipital Bone ◽

High Rate ◽

Type C ◽

The Brain ◽

Rate Of Improvement

Abstract Introduction We classified Chiari malformation type I (CM-I) according to the mechanism of ptosis of the brain stem and cerebellum, based on a morphometric study of the posterior cranial fossa (PCF) and craniovertebral junction (CVJ). Surgery was performed to manage the mechanism of the hindbrain ptosis. Materials and Methods We calculated the volume of the PCF (VPCF) and the area surrounding the foramen magnum (VSFM) and measured the axial length of the enchondral parts of the occipital bone (occipital bone size) and the hindbrain. According to these measures, we classified CM-I into type A (normal VPCF, normal VSFM, and normal occipital bone size), type B (normal VPCF, small VSFM, and small occipital bone size), and type C (small VPCF, small VSFM, and small occipital bone size). Foramen magnum decompression (FMD) (280 cases) was performed on CM-I types A and B. Expansive suboccipital cranioplasty (ESCP) was performed on CM-I type C. Posterior craniocervical fixation (CCF) was performed in cases with CVJ instability. Lysis of the adhesion and/or sectioning of the filum terminale were performed on cases with tethered cord syndrome. Results Both ESCP and FMD had a high rate of improvement of neurological symptoms (87%) and recovery rate. There was only small number of complications. CCF had a high rate of improvement of neurological symptoms (88%) and joint stabilization. Conclusion In the management of Chiari malformation, appropriate surgical methods that address ptosis of the hindbrain should be chosen. Each surgical approach resulted in a good improvement of neurological symptoms.

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Clinical and Molecular Features of Early Infantile Niemann Pick Type C Disease

International Journal of Molecular Sciences ◽

10.3390/ijms21145059 ◽

2020 ◽

Vol 21 (14) ◽

pp. 5059 ◽

Cited By ~ 2

Author(s):

Berna Seker Yilmaz ◽

Julien Baruteau ◽

Ahad A. Rahim ◽

Paul Gissen

Keyword(s):

Neurological Symptoms ◽

Novel Therapy ◽

Clinical Patient ◽

Molecular Features ◽

Niemann Pick Disease ◽

Exon 1 ◽

Type C ◽

Vertical Supranuclear Gaze Palsy ◽

Niemann Pick ◽

Prolonged Jaundice

Niemann Pick disease type C (NPC) is a neurovisceral disorder due to mutations in NPC1 or NPC2. This review focuses on poorly characterized clinical and molecular features of early infantile form of NPC (EIF) and identified 89 cases caused by NPC1 (NPC1) and 16 by NPC2 (NPC2) mutations. Extra-neuronal features were common; visceromegaly reported in 80/89 NPC1 and in 15/16 NPC2, prolonged jaundice in 30/89 NPC1 and 7/16 NPC2. Early lung involvement was present in 12/16 NPC2 cases. Median age of neurological onset was 12 (0–24) and 7.5 (0–24) months in NPC1 and NPC2 groups, respectively. Developmental delay and hypotonia were the commonest first detected neurological symptoms reported in 39/89 and 18/89 NPC1, and in 8/16 and 10/16 NPC2, respectively. Additional neurological symptoms included vertical supranuclear gaze palsy, dysarthria, cataplexy, dysphagia, seizures, dystonia, and spasticity. The following mutations in homozygous state conferred EIF: deletion of exon 1+promoter, c.3578_3591 + 9del, c.385delT, p.C63fsX75, IVS21-2delATGC, c. 2740T>A (p.C914S), c.3584G>T (p.G1195V), c.3478-6T>A, c.960_961dup (p.A321Gfs*16) in NPC1 and c.434T>A (p.V145E), c.199T>C (p.S67P), c.133C>T (p.Q45X), c.141C>A (p.C47X) in NPC2. This comprehensive analysis of the EIF type of NPC will benefit clinical patient management, genetic counselling, and assist design of novel therapy trials.

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