ABSTRACT
Lewy bodies are intraneuronal eosinophilic cytoplasmic inclusions, and their presence in the specific areas of the central nervous system defines the so-called Lewy body disorders such as Parkinson's disease and dementia with Lewy bodies. The protein alpha-synuclein is the major component of Lewy bodies and there is evidence suggesting that it is capable of spreading from cell to cell within the central nervous system thereby propagating the pathological process. The olfactory system, particularly the olfactory bulb, is almost always affected in Parkinson's disease and dementia with Lewy bodies. Moreover, in Parkinson's disease, the olfactory bulb is involved by Lewy pathology at very early stages of the disease. The hypothalamus is also compromised by Lewy pathology in the course of Parkinson's disease; however, unlike the olfactory system in which most regions of the primary olfactory cortex become affected, there is a selective vulnerability of certain hypothalamic regions including the tuberomamillary nucleus, the lateral tuberal nucleus, and orexin/hypocretin neurons, while other nuclear groups remain free of Lewy pathology even in the advanced stages of the disease.
Subject(s)
Lewy Body Disease , Parkinson Disease , Humans , Hypothalamus/metabolism , Lewy Bodies , alpha-Synuclein/metabolismSubject(s)
Brain Diseases/etiology , Brain Diseases/therapy , Cysts/etiology , Deep Brain Stimulation/adverse effects , Electrodes, Implanted/adverse effects , Postoperative Complications , Brain Diseases/surgery , Cysts/diagnostic imaging , Cysts/surgery , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Parkinson Disease/therapy , Stereotaxic TechniquesABSTRACT
Olfactory limbic structures, like the amygdala, the entorhinal, and the piriform cortices, are closely involved in cognitive processes. Thus, besides olfactory dysfunctions, it is conceivable that the compromise of these structures can lead to cognitive impairment. The olfactory bulb is affected by alpha-synuclein pathology in almost all cases of both Parkinson's disease and dementia with Lewy bodies. The clinical distinction between these disorders relies on the timing in the appearance of dementia in relationship to motor symptoms. Typically, it occurs late in the course of Parkinson's disease, and within the first year in dementia with Lewy bodies. The close anatomical proximity of the olfactory bulb with limbic regions, together with the early occurrence of cognitive impairment that is observed in dementia with Lewy bodies, raise the question whether the propagation of alpha-synuclein pathology in this condition might originate in the olfactory bulb, spreading from there to other limbic structures, and thereby reaching the associative neocortex. This review will describe the anatomical basis of the olfactory system and discuss the evidence of potential spreading pathways from the olfactory bulb that could support the presence of early dementia in the setting of Lewy body disorders.
Subject(s)
Lewy Body Disease/metabolism , Lewy Body Disease/pathology , Olfactory Bulb/metabolism , Olfactory Bulb/pathology , alpha-Synuclein/metabolism , Animals , Disease Models, Animal , Humans , Models, BiologicalABSTRACT
The diagnosis of Parkinson's disease (PD) relies on clinical features whereas pathological confirmation is only possible with autopsy examination. The neuropathological hallmarks of PD are neuronal loss and the presence of inclusions termed Lewy bodies/neurites in affected regions. A major component of these inclusions is phosphorylated alpha-synuclein (α-SYN) protein. There is evidence that α-SYN pathology is widely distributed outside the central nervous system in patients with PD. The gastrointestinal tract is importantly affected by α-SYN containing inclusions and typically there is a rostrocaudal gradient for the distribution of the pathology. The highest amounts of Lewy bodies/neurites are found at the submandibular gland together with the lower esophagus and the lowest amounts are found in the rectum. Autopsy findings prompted research aimed at achieving in vivo pathological diagnosis of PD by demonstrating the presence of α-SYN pathology in biopsy material of these peripheral accessible tissues. So far, biopsy studies of the gut have demonstrated the presence of α-SYN pathology in the salivary glands, stomach, duodenum, colon, and rectum. Further research is necessary in order to determine which are the most sensitive targets for in vivo α-SYN pathology detection and the safest techniques for these approaches in patients with PD.
ABSTRACT
The recent demonstration of the presence of Lewy pathology in the submandibular glands of Parkinson's disease (PD) patients prompted us to evaluate the diagnostic performance of minor salivary gland biopsy for PD. Minor salivary glands were examined for Lewy pathology using phosphorylated alpha-synuclein antibody in 16 patients with clinically diagnosed PD and 11 control subjects with other neurological disorders. Abnormal accumulation of alpha-synuclein was found in 3 out of 16 PD patients. Two control subjects exhibited weak phosphorylated alpha-synuclein immunoreactivity. Our results do not support the use of minor salivary glands biopsy for the detection of Lewy pathology in living subjects.
Subject(s)
Lewy Bodies/pathology , Parkinson Disease/pathology , Salivary Glands, Minor/pathology , Aged , Aged, 80 and over , Biopsy , Female , Humans , Male , Middle AgedABSTRACT
A 22-year-old man presented with a 2-year history of tremor of the upper limbs associated to behavioral disorders. A magnetic resonance imaging of the brain showed hyperintensity in the right frontoparietal region, basal ganglia, particularly in the caudate nucleus, midbrain, and pons in T2 sequences, fluid-attenuated inversion recovery, and diffusion. Serum ceruloplasmin levels were 4 mg/dL (range, 20-45 mg/dL), and 24-hour urine cooper excretion was increased up to 223 µg (10-40 µg/24 hours). Slit lamp examination demonstrated the presence of a Kayser-Fleischer ring and penicillamine treatment started. Four months later, he developed episodes of paroxysmal dystonic posturing of his left arm, which increased in frequency reaching 2 or 3 attacks per hour. They were triggered by voluntary movements and forced him to adopt an abnormal flexion of the left forearm over the left bicep and were preceded by a tightening sensation of the left forearm muscles. Episodes completely remitted with oxcarbazepine.
Subject(s)
Carbamazepine/analogs & derivatives , Dystonia/diagnosis , Hepatolenticular Degeneration/diagnosis , Penicillamine/adverse effects , Carbamazepine/therapeutic use , Dystonia/chemically induced , Dystonia/drug therapy , Hepatolenticular Degeneration/drug therapy , Humans , Male , Movement Disorders/diagnosis , Movement Disorders/drug therapy , Oxcarbazepine , Young AdultABSTRACT
We report the case of a 76-year-old, right-handed woman with progressive primary freezing of gait. Despite several therapeutic strategies, she continued to worsen to the point that she became confined to a wheelchair. Treatment with selegiline in doses up to 20 mg/d led to marked improvement of the gait disorder. This case illustrates that selegiline can be an option for patients with freezing of gait other than those with Parkinson's disease.
Subject(s)
Freezing Reaction, Cataleptic/drug effects , Gait Disorders, Neurologic/drug therapy , Neuroprotective Agents/therapeutic use , Selegiline/therapeutic use , Aged , Dose-Response Relationship, Drug , Female , HumansABSTRACT
A 47-year-old patient with hereditary spastic paraplegia and parkinsonian features is reported. Treatment with levodopa led to marked improvement in his neurological status and quality of life. However, several years later he developed motor fluctuations and dyskinesias. The latter promptly remitted with amantadine treatment.
Subject(s)
Antiparkinson Agents/therapeutic use , Levodopa/therapeutic use , Parkinson Disease/drug therapy , Parkinson Disease/etiology , Spastic Paraplegia, Hereditary/complications , Follow-Up Studies , Humans , Male , Middle Aged , Spastic Paraplegia, Hereditary/drug therapyABSTRACT
Hemimasticatory spasm (HMS) is a rather uncommon movement disorder with a pathophysiology that is still unclear, although temporomasseter entrapment at the temporal fossa has been advanced. The authors present a case of HMS in a woman who experienced marked worsening in episode frequency and severity during pregnancy. Treatment with botulinum toxin led to marked improvement.
Subject(s)
Anti-Dyskinesia Agents/therapeutic use , Botulinum Toxins/therapeutic use , Hemifacial Spasm/drug therapy , Pregnancy Complications/drug therapy , Adult , Dose-Response Relationship, Drug , Electromyography/methods , Female , Humans , Masticatory Muscles/drug effects , Masticatory Muscles/physiopathology , PregnancyABSTRACT
Movement disorders are commonly encountered in clinical practice. The diagnosis of movement disorders relies on a focused history and neurologic examination. Diagnostic steps include (1) identification of the phenomenology of the movements (eg, tremor); (2) characterization of appropriate clinical syndromes; and (3) differential diagnosis of specific disease entities. Accurate diagnosis is essential because symptomatic treatment exists for most movement disorders.
Subject(s)
Huntington Disease/diagnosis , Lewy Body Disease/diagnosis , Multiple System Atrophy/diagnosis , Myoclonus/diagnosis , Myoclonus/physiopathology , Parkinson Disease/diagnosis , Spine/physiopathology , Torticollis/diagnosis , Tourette Syndrome/diagnosis , Tremor/diagnosis , Tremor/psychology , Adult , Aged , Anticonvulsants/therapeutic use , Atrophy/pathology , Brain/pathology , Child , Clonazepam/therapeutic use , Diagnosis, Differential , Female , Humans , Male , Middle Aged , Myoclonus/drug therapy , Neurologic Examination , Parkinson Disease/drug therapy , Torticollis/drug therapy , Tourette Syndrome/drug therapy , Treatment Failure , Tremor/drug therapyABSTRACT
The safety and tolerability of quetiapine (up to 75 mg/day) as monotherapy on essential tremor were investigated in an open-label study in 10 patients. Five men and 5 women, with a mean age of 66.3 years, affected by essential tremor participated in the trial. They were treated with increasing doses of quetiapine to 75 mg/day over a 6-week period. Side effects included a paradoxical psychiatric reaction in one and anger in another, and in both cases quetiapine was discontinued. In two other patients, somnolence led to dose reduction. There were no pre- versus post-treatment differences, but 3 out of 10 patients benefited (improvement >20%). Although the study was not powered to assess efficacy, quetiapine seems to be a safe drug for the treatment of essential tremor.
Subject(s)
Antipsychotic Agents/therapeutic use , Dibenzothiazepines/therapeutic use , Essential Tremor/drug therapy , Aged , Aged, 80 and over , Analysis of Variance , Dose-Response Relationship, Drug , Female , Humans , Male , Middle Aged , Neuropsychological Tests , Psychiatric Status Rating Scales , Quetiapine Fumarate , Treatment OutcomeABSTRACT
A human immunodeficiency virus-positive patient receiving indinavir therapy developed a slowly progressive paraparesis. Magnetic resonance imaging findings were consistent with epidural lipomatosis. On discontinuing indinavir, symptoms gradually remitted. Although indinavir, a protease inhibitor, is known to cause abnormal fat accumulation, to the best of our knowledge this is the first report of epidural lipomatosis.
