Learn more about Cerebellar Stroke at TriStar Southern Hills DefinitionCausesRisk FactorsSymptomsDiagnosisTreatmentPreventionrevision ...
Illustration for the article: Remote cerebellar haemorrhage. Funes T, González Abbati S, Clar F, Zaninovich R, Mormandi R, Stella O. Rev Argent Neuroc 2010.
ataxia consist of gait impairment, unclear ("scanning") speech, visual blurring due to nystagmus, hand incoordination, and tremor with movement. These result from the involvement of the cerebellum and its afferent and efferent pathways, including the spinocerebellar pathways, and the frontopontocerebellar pathway originating in the rostral frontal lobe. True cerebellar ataxia must be distinguished from ataxia associated with vestibular nerve or labyrinthine disease, as the latter results in a disorder of gait associated with a significant degree of dizziness, light-headedness, or the perception of movement (Chap. 21). True cerebellar ataxia is devoid of these vertiginous complaints and is clearly an unsteady gait due to imbalance. Sensory disturbances can also on occasion simulate the imbalance of cerebellar disease; with sensory ataxia, imbalance dramatically worsens when visual input is removed (Romberg sign). Rarely, weakness of proximal leg muscles mimics cerebellar disease. In the patient ...
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The cerebellum, principally a motor organ, is responsible for the coordination of movements, especially skilled voluntary ones, the control of posture and gait, and the regulation of muscular tone. In the last decade it has come to be appreciated that the cerebellum may play a role in the modulation of the emotional state and some aspects of cognition. The mechanisms by which these functions are accomplished have been the subject of intense investigation by anatomists and physiologists. Their studies have yielded a mass of data, testimony to the complexity of the organization of the cerebellum and its afferent and efferent connections. A coherent picture of cerebellar function is now emerging, although it is not yet possible, with a few notable exceptions, to relate each of the symptoms of cerebellar disease to a derangement of a discrete anatomic or functional unit of the cerebellum. ...
The term diaschisis refers to a neural dysfunction manifesting in anatomically intact, but functionally related, brain regions distant from a primary lesion. Here we report the diaschisis phenomenon as a consequence of a first demyelinating event in the middle and superior cerebellar peduncles in both the ipsilateral cerebellar hemisphere and in the contralateral thalamus and cerebral cortex (two-way crossed cerebellar diaschisis), resulting in the simultaneous disruption of the afferent cortico-ponto-cerebellar pathway and the efferent cerebellar-thalamo-cortical pathway. The use of 18F-FDG-PET could help clarifying in vivo the distant pathophysiological effect of focal lesions in inflammatory diseases such as multiple sclerosis.. ...
List of 61 causes for Cerebellar lesions and Osteomyelitis and Unusual sputum odour in children, alternative diagnoses, rare causes, misdiagnoses, patient stories, and much more.
It is widely accepted that action and perception in humans functionally interact on multiple levels. Moreover, areas originally suggested to be predominantly motor-related, as the cerebellum, are also involved in action observation. However, as yet, few studies provided unequivocal evidence that the cerebellum is involved in the action perception coupling (APC), specifically in the integration of motor and multisensory information for perception. We addressed this question studying patients with focal cerebellar lesions in a virtual-reality paradigm measuring the effect of action execution on action perception presenting self-generated movements as point lights. We measured the visual sensitivity to the point light stimuli based on signal detection theory. Compared with healthy controls cerebellar patients showed no beneficial influence of action execution on perception indicating deficits in APC. Applying lesion symptom mapping, we identified distinct areas in the dentate nucleus and the ...
While gray matter volume increase was larger in cerebral areas in patients compared with controls, the opposite was found in the cerebellum, with a more pronounced increase in gray matter volume in controls compared with patients. This implies that motor improvements in patients with cerebellar degeneration appear to be driven by cerebral structures unaffected by the disease. In both cerebellar patients and controls, gray matter changes were found in supratentorial areas known to contribute to various aspects and stages of motor learning. In cerebellar patients, most changes were observed in the frontal cortex, whereas gray matter changes in occipitotemporal areas and basal ganglia prevailed in healthy controls.. We found no evidence to substantiate the claim that cerebellar patients increasingly recruit the basal ganglia circuits to compensate for their motor deficit (Wessel et al., 1995). In the patient group, the most compelling change in gray matter volume was seen in the dorsal premotor ...
The cerebellum: Once the movement of the arm is initiated, sensory information is needed to guide the finger to its precise destination. In addition to sight, the most important source of information comes from the "position sense" provided by the many sensory neurons located within the limbs (proprioception). Proprioception is what allows an individual to touch their nose with their finger even with the eyes closed. The balance organs in the ears provide important information about posture. Both postural and proprioceptive information are processed by a structure at the rear of the brain called the cerebellum. The cerebellum sends out electrical signals to modify movements as they progress, organizing the voluntary commands into a tightly controlled pattern. Cerebellar disorders cause ataxia (inability to control the force, fine positioning, and speed of movements). Disorders of the cerebellum may also impair the ability to judge distance so that a person under- or overreaches the target ...
Background and purpose Arterial spin-labeling (ASL) was recently introduced as a noninvasive method to evaluate cerebral hemodynamics. The purposes of this study were to assess the ability of ASL imaging to detect crossed cerebellar diaschisis (CCD) in patients with their first unilateral supratentorial hyperacute stroke and to identify imaging or clinical factors significantly associated with CCD. Materials and methods We reviewed 204 consecutive patients who underwent MRI less than 8 hours after the onset of stroke symptoms. The inclusion criteria were supratentorial abnormality in diffusion-weighted images in the absence of a cerebellar or brain stem lesion, bilateral supratentorial infarction, subacute or chronic infarction, and MR angiography showing vertebrobasilar system disease. For qualitative analysis, asymmetric cerebellar hypoperfusion in ASL images was categorized into 3 grades. Quantitative analysis was performed to calculate the asymmetric index (AI). The patients demographic and
Cerebellum & Ataxias, sister journal to The Cerebellum, is an open access journal devoted to cerebellar research and cerebellar disorders, including ...
Cerebellum & Ataxias, sister journal to The Cerebellum, is an open access journal devoted to cerebellar research and cerebellar disorders, including ...
Three neuropsychological experiments on a group of 16 cerebellar patients and 16 age-and education-matched controls investigated the effects of damage to the cerebellum on English grammatical morphology across production, comprehension, and grammaticality judgment tasks. In Experiment 1, participants described a series of pictures previously used in studies of cortical aphasic patients. The cerebellar patients did not differ significantly from the controls in the total number of words produced or in the proportion of closed-class words. They did differ to a marginally significant extent in the production of required articles. In Experiment 2, participants identified the agent in a series of aurally presented sentences in which three agency cues (subject-verb agreement, word order, and noun animacy) were manipulated. The cerebellar patients were less affected than the controls were by the manipulation of subject-verb agreement to a marginally significant extent. In Experiment 3, participants ...
Spinocerebellar ataxia 42 (SCA42) [MIM:616795]: A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA42 is a slowly progressive, autosomal dominant form with variable severity. {ECO:0000269,PubMed:26456284, ECO:0000269,PubMed:26715324}. Note=The disease is caused by mutations affecting the gene represented in this entry ...
Neurodegenerative diseases (NDD) are a group of illness with diverse clinical importance and etiologies. NDD include motor neuron disease such as amyotrophic lateral sclerosis (ALS), cerebellar disorders, Parkinsons disease (PD), Huntingtons disease (HD), cortical destructive Alzheimers disease ( …
Inclusion Criteria: - Age ≥18 years - Acute cerebral ischemia due to occlusion of the internal carotid or middle cerebral artery - NIHSS 8-25 (inclusive) - Persistent arterial occlusion (defined as TICI 0 or 1) following failed mechanical revascularization (ref Table 2) - Able to undergo NeuroFlo treatment within 18 hours of symptom onset (or from last time known normal) - Informed consent from patient or legally authorized representative - Negative pregnancy test in females of child-bearing potential Exclusion Criteria: - Etiology other than cerebral ischemia - Acute hypodense parenchymal lesion or effacement of cerebral sulci in more than 1/3 of the middle cerebral artery territory - Brainstem or cerebellar stroke - Systolic blood pressure (BP) >220 mm Hg, or diastolic (BP) >140 mm Hg that cannot be lowered with medical management - Any use of intravenous or intra-arterial thrombolytic medication - Known secured or unsecured cerebral aneurysm or vascular malformation on CTA or MRA or history ...
A role for the cerebellum in cognition has been proposed based on studies suggesting a profile of cognitive deficits due to cerebellar stroke. Such studies are limited in the determination of the detailed organisation of cerebellar subregions that ar
Stroke Survivors is a website for stroke victims, particularly Cerebellar stroke victims who are in a minority. However any stroke victim should find some useful information, at least that is my intention. The site was developed and is maintained by myself; John DArcy
Stroke Survivors is a website for stroke victims, particularly Cerebellar stroke victims who are in a minority. However any stroke victim should find some useful information, at least that is my intention. The site was developed and is maintained by myself; John DArcy
The item is aimed at finding evidence of a unilateral cerebellar lesion. Test with eyes open. In case of visual defect, ensure testing is done in intact visual field. The finger-nose-finger and heel-shin tests are performed on both sides, and ataxia is scored only if present out of proportion to weakness. Ataxia is absent in the patient who cannot understand or is paralyzed. Only in the case of amputation or joint fusion, the examiner should record the score as untestable (UN), and clearly write the explanation for this choice. In case of blindness, test by having the patient touch nose from extended arm position ...
We know that when the cerebellum is damaged, it causes movement disorders in both speech and non-speech actions," says UW-Madison Waisman Center investigator Ben Parrell. "What we dont understand is why cerebellar damage leads to these disorders.". So Parrell, who is a new assistant professor of communication sciences and disorders at UW-Madison, set out to investigate.. In a recent study, he and his colleagues discovered that damage to the cerebellum diminishes our ability to predict consequences of an action and issue specific motor commands to the body - what researchers call "feedforward control.". Diminished feedforward - or predictive - control could explain speech difficulties often faced by individuals with cerebellar damage.. "If you can correctly predict what will happen after an action - like trying to say a specific word, for example - you can do things more fluidly, more rapidly because you dont need to monitor outcomes in real time," says Parrell.. In contrast, without properly ...
The timing and duration of alcohol exposure was manipulated in neonatal rats by using a binge model of alcohol exposure during the third trimester equivalent. Groups of Sprague-Dawley rats were exposed to binges via artificial rearing on postnata
Jun Hu, Jin Qian, Oleg Borisov, Sanqiang Pan, Yan Li, Tong Liu, Longwen Deng, Kenneth Wannemacher, Michael Kurnellas, Christa Patterson, Stella Elkabes, Hong Li
The cerebellum has been considered only as a classical subcortical center for motor control. However, accumulating experimental and clinical evidences have revealed that the cerebellum also plays an important role in cognition, for instance, in learning and memory, as well as in emotional behavior and in nonsomatic activities, such as visceral and immunological responses. Although it is not yet clear through which pathways such cerebellar nonsomatic functions are mediated, the direct bidirectional connections between the cerebellum and the hypothalamus, a high autonomic center, have recently been demonstrated in a series of neuroanatomical investigations on a variety of mammals and indicated to be potential pathways underlying the cerebellar autonomic modulation. The direct hypothalamocerebellar projections originate from the widespread hypothalamic nuclei/areas and terminate in both the cerebellar cortex as multilayered fibers and the cerebellar nuclei. Immunohistochemistry studies have offered ...
Question - Suffered a brain stroke, vomiting tendency. MRI shows acute cerebellar infarcts. How to cure nausea?. Ask a Doctor about uses, dosages and side-effects of Ondansetron, Ask a Neurologist
49yr old man with pT4 Sq cell cancer, post adjuvant chemotherapy for local RT detected to have cerebellar lesion , radically treated, ? role of adjuvant RT to the primary tumour bed ...
University of Bristol - person profile - Bristol Neuroscience - Professor Richard Apps - Cerebellar contributions to movement control
Title:Aminopyridines and Acetyl-DL-leucine: New Therapies in Cerebellar Disorders. VOLUME: 17 ISSUE: 1. Author(s):Roger Kalla and Michael Strupp*. Affiliation:Department of Neurology, German Center for Vertigo and Balance Disorders, and Institute for Clinical Neurosciences, University Hospital Munich, Campus Grosshadern, Munich, Department of Neurology, German Center for Vertigo and Balance Disorders, and Institute for Clinical Neurosciences, University Hospital Munich, Campus Grosshadern, Munich. Keywords:Cerebellar ataxia, central vestibular disorders, aminopyridines, 4-aminopyridine, episodic ataxia type 2, downbeat nystagmus, acetyl-DL-leucine.. Abstract:Cerebellar ataxia is a frequent and often disabling syndrome severely impairing motor functioning and quality of life. Patients suffer from reduced mobility, and restricted autonomy, experiencing an even lower quality of life than, e.g., stroke survivors. Aminopyridines have been demonstrated viable for the symptomatic treatment of certain ...
TY - GEN. T1 - Landmark based shape analysis for cerebellar ataxia classification and cerebellar atrophy pattern visualization. AU - Yang, Zhen. AU - Abulnaga, S. Mazdak. AU - Carass, Aaron. AU - Kansal, Kalyani. AU - Jedynak, Bruno M.. AU - Onyike, Chiadikaobi U. AU - Ying, Sarah H.. AU - Prince, Jerry Ladd. PY - 2016. Y1 - 2016. N2 - Cerebellar dysfunction can lead to a wide range of movement disorders. Studying the cerebellar atrophy pattern associated with different cerebellar disease types can potentially help in diagnosis, prognosis, and treatment planning. In this paper, we present a landmark based shape analysis pipeline to classify healthy control and different ataxia types and to visualize the characteristic cerebellar atrophy patterns associated with different types. A highly informative feature representation of the cerebellar structure is constructed by extracting dense homologous landmarks on the boundary surfaces of cerebellar sub-structures. A diagnosis group classifier based on ...
Acute cerebellitis and acute cerebellar ataxia represent a spectrum of inflammatory processes characterized by sudden onset cerebellar dysfunction. It usually affects children and is related as a consequence of primary or secondary infection, or ...
From UniProt:. Spinocerebellar ataxia, autosomal recessive, 13 (SCAR13): A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR13 is characterized by delayed psychomotor development beginning in infancy. Affected individuals show mild to profound mental retardation with poor or absent speech as well as gait and stance ataxia and hyperreflexia. [MIM:614831]. Spinocerebellar ataxia 44 (SCA44): A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA44 is a slowly ...
The spinocerebellar ataxias (SCAs) are a genetically heterogeneous group of dominantly inherited progressive ataxia disorders. More than 30 different gene loci have been identified so far. The most common SCAs, which together account for more than half of all affected families, are SCA1, SCA2, SCA3, and SCA6. Each of these disorders is caused by a translated CAG repeat expansion mutation. SCA1, SCA2, and SCA3 usually have an onset between 30 and 40, and SCA6 usually begins at the age of 50 to 60. In addition to progressive ataxia, SCA1, SCA2, and SCA3 frequently present with additional non-ataxic symptoms, including parkinsonism. Carbidopa/levodopa was found to have a good therapeutic effect on parkinsonism.. The SCA6 used to be considered a pure cerebellar disorder. However, a recent large study on natural history of SCAs found that patients with SCA6 often had nonataxia symptoms, an observation that challenges the view that SCA6 is a purely cerebellar disorder. Parkinsonism in SCA6 was rarely ...
Growing chicks maintained on a diet consisting of milk powder, casein, starch, yeast, cod liver oil, salts and filter paper develop ataxia, tremors, retraction or twisting of the head, clonic spasms of the legs, and stupor. These symptoms may appear suddenly, usually between the 18th and 25th day, and may end in death. If recovery takes place, the chicks may go on to normal development.. Definite lesions are found in the cerebellum of the affected chicks. These consist of edema, necrosis and hemorrhages. Hyaline thrombi are found in the capillaries in and about the degenerated areas.. ...
The staggerer mutant mouse carries a spontaneous mutation in the ligand-binding domain of the rora gene. RORα is expressed in many tissues and its loss leads to diverse abnormalities. In the cerebellu
We present a 7-year-old boy with acute cerebellitis who required an emergency ventriculoperitoneal shunt for hydrocephalus caused by cerebellar swelling. This represents a very unusual, potentially life-threatening complication of a usually self-limiting condition. Early diagnosis of this complication is essential in view of the propensity to sudden and fatal deterioration. Magnetic resonance imaging (MRI) is useful in differentiating this unusual course of acute cerebellar ataxia from that of a posterior fossa tumor. In developing countries, however, computed tomography (CT) is often the only existing diagnostic modality and access to MRI, when available, is limited. Our case demonstrates that the shape of the fourth ventricle on CT can be helpful in differentiating between a tumor and edema of the cerebellum and thus can assist in management ...
TY - JOUR. T1 - Cerebellar involvement in multifocal eosinophilic granuloma. T2 - Demonstration by computerized tomographic scanning. AU - Adornato, B. T.. AU - Eil, C.. AU - Head, G. L.. AU - Loriaux, Donald (Lynn). PY - 1980. Y1 - 1980. N2 - Central nervous system involvement outside the hypothalamus or pituitary in multifocal eosinophilic granuloma (MEG) is unusual. Eleven patients with MEG have been examined with cranial computerized axial tomograms (CT). Four patients with moderate to severe cerebellar dysfunction, 3 of whom had no detectable lesions by other neuroradiological techniques, were found to have cerebellar abnormalities. All of the remaining 7 patients with normal neurological examinations had normal CT scans. Computerized axial tomography is a useful technique in the evaluation of patients with MEG and neurological impairment.. AB - Central nervous system involvement outside the hypothalamus or pituitary in multifocal eosinophilic granuloma (MEG) is unusual. Eleven patients ...
Results There were 383 patients with Friedreichs ataxia (FRDA), 205 patients with SCA and 168 controls. In FRDA, 31% of the variance of cerebellar signs with the CCFS and 41% of that with SARA were explained by disease duration, age at onset and the shorter abnormal repeat in the FXN gene. Increases in CCFS and SARA scores per year were lower for FRDA than for SCA (CCFS index: 0.123±0.123 per year vs 0.163±0.179, P,0.001; SARA index: 1.5±1.2 vs 1.7±1.7, P,0.001), indicating slower cerebellar dysfunction indexes for FRDA than for SCA. Patients with SCA2 had higher CCFS scores than patients with SCA1 and SCA3, but similar SARA scores. ...
Cerebellar atrophy caused by Dilantin. Damage to the cerebellum results in lack of balance, slow movements. Severe atrophy linked to long term use of Dilantin. cerebellar degeneration include seizures
Cerebellar atrophy caused by Dilantin. Damage to the cerebellum results in lack of balance, slow movements. Severe atrophy linked to long term use of Dilantin. cerebellar degeneration include seizures
are described, all of which show no change in intensity exponential time-course withdecreasing velocity. This waveform with the removal of visual fixation in contrast to periph- eral vestibular nystagmus. Downbeat nystagmus may or may not be present in the primary position. It beats impaired neural integrator. (c)Drift of the eyes away from the directly downwards and is often accentuated in lateral gaze. When present in the primary position a disturbance of the vestibulocerebellum, drug intoxication or an (increasing velocity). Thiswaveform suggests an unstable abnormality at the cranio-cervical junction, such as a Type 1 Chiari malformation, are usually found6. These causes include cerebellar degenerations, anticonvulsant drugs, lithium intoxication and intra-axial brainstem vertically in cerebellar disease. (d)Pendular nystagmus, which is lesions. In about half of the patients with downbeat nys- tagmus, no cause can be found. Treatment can be attempted with clonazepam, baclofen, ...
Joubert syndrome is a rare autosomal recessive genetic disorder that affects the cerebellum, an area of the brain that controls balance and coordination. Joubert syndrome is one of the many genetic syndromes associated with syndromic retinitis pigmentosa. The syndrome was first identified in 1969 by pediatric neurologist Marie Joubert in Montreal, Quebec, Canada, while working at the Montreal Neurological Institute and McGill University. Most of the signs and symptoms of the Joubert syndrome appear very early in infancy with most children showing delays in gross motor milestones. Although other signs and symptoms vary widely from individual to individual, they generally fall under the hallmark of cerebellum involvement or in this case, lack thereof. Consequently, the most common features include ataxia (lack of muscle control), hyperpnea (abnormal breathing patterns), sleep apnea, abnormal eye and tongue movements, and hypotonia in early childhood. Other malformations such as polydactyly (extra ...
For many degenerative cerebellar diseases, currently, no effective treatment that would substantially restore cerebellar functions is available. Neurotransplantation could be a promising therapy for...
Dizziness, Nystagmus, Obstructive Hydrocephalus Symptom Checker: Possible causes include Arnold Chiari Malformation, Cerebellar Stroke, Cerebellar Hemorrhage. Check the full list of possible causes and conditions now! Talk to our Chatbot to narrow down your search.
The cerebellum and the motor thalamus, connected by cerebellothalamic pathways, are traditionally considered part of the motor-control system. Yet, functional imaging studies and clinical studies including patients with cerebellar disease suggest an involvement of the cerebellum in olfaction. Additionally, there are anecdotal clinical reports of olfactory disturbances elicited by electrical stimulation of the motor thalamus and its neighbouring subthalamic region. Deep brain stimulation (DBS) targeting the cerebellothalamic pathways is an effective treatment for essential tremor (ET), which also offers the possibility to explore the involvement of cerebellothalamic pathways in the sense of smell. This may be important for patient care given the increased use of DBS for the treatment of tremor disorders. Therefore, 21 none-medicated patients with ET treated with DBS (13 bilateral, 8 unilateral) were examined with "Sniffin Sticks," an established and reliable method for olfactory testing. ...
Cerebellar neurons are generated from two germinal neuroepithelia: the ventricular zone (VZ) and rhombic lip. Signaling mechanisms that maintain the proliferative capacity of VZ resident progenitors remain elusive. We reveal that Sonic hedgehog (Shh) signaling is active in the cerebellar VZ and essential to radial glial cell proliferation and expansion of GABAergic interneurons. We demonstrate that the cerebellum is not the source of Shh that signals to the early VZ, and suggest a transventricular path for Shh ligand delivery. In agreement, we detected the presence of Shh protein in the circulating embryonic cerebrospinal fluid. This study identifies Shh as an essential proliferative signal for the cerebellar ventricular germinal zone, underscoring the potential contribution of VZ progenitors in the pathogenesis of cerebellar diseases associated with deregulated Shh signaling, and reveals a transventricular source of Shh in regulating neural development.. ...
When I left Goroka I stopped in Port Moresby, where I had the opportunity to meet Jettie and Vin Zigas. Vin had been an Australian medical officer in the highlands and was the first physician to study kuru in some detail (figure 1b). In 1957, he was joined by Gajdusek and, together, they wrote two landmark papers on the disease (Gajdusek & Zigas 1957; Zigas & Gajdusek 1957). I chose not to discuss with Vin my clinical findings indicating that kuru patients did not show signs of parkinsonism as he and Gajdusek had thought when they first described kuru. I rapidly developed a warm friendship with Vin and Jettie.. When I returned to New Guinea in 1980, I had the pleasure of meeting Michael Alpers, which marked the beginning of a long friendship. As with my first trip, my guides were Anua and Auyana. Together we saw an additional seven patients whose clinical examinations confirmed my previous impressions. Kuru was a cerebellar disease that eventually progressed to involve other parts of the central ...
Purkinje cell axonal swellings (torpedoes), described in several cerebellar disorders as well as essential tremor (ET), have not been quantified in common neurodegenerative conditions.
Diagnosis of neurological disease -- Episodic impairment of consciousness -- Falls and drop attacks -- Delirium -- Stupor and coma -- Brain death, vegetative state, and minimally conscious states -- Intellectual and memory impairments -- Global developmental delay and regression -- Behavior and personality disturbances -- Depression and psychosis in neurological practice -- Limb apraxias and related disorders -- Agnosias -- Aphasia and aphasic syndromes -- Dysarthria and apraxia of speech -- Neurogenic dysphagia -- Visual loss -- Abnormalities of the optic nerve and retina -- Pupillary and eyelid abnormalities -- Disturbances of smell and taste -- Cranial and facial pain -- Brainstem syndromes -- Ataxic and cerebellar disorders -- Diagnosis and assessment of Parkinson disease and other movement disorders -- Gait disorders -- Hemiplegia and monoplegia -- Paraplegia and spinal cord syndromes -- Proximal, distal, and generalized weakness -- Muscle pain and cramps -- Hypotonic (floppy) infant -- ...
The molecular basis of nephronophthisis, the most frequent genetic cause of renal failure in children and young adults, and its association with retinal degeneration and cerebellar vermis aplasia in Joubert syndrome are poorly understood. Using positional cloning, we here identify mutations in the gene CEP290 as causing nephronophthisis. It encodes a protein with several domains also present in CENPF, a protein involved in chromosome segregation. CEP290 (also known as NPHP6) interacts with and modulates the activity of ATF4, a transcription factor implicated in cAMP-dependent renal cyst formation. NPHP6 is found at centrosomes and in the nucleus of renal epithelial cells in a cell cycle-dependent manner and in connecting cilia of photoreceptors. Abrogation of its function in zebrafish recapitulates the renal, retinal and cerebellar phenotypes of Joubert syndrome. Our findings help establish the link between centrosome function, tissue architecture and transcriptional control in the pathogenesis ...