Atypical Parkinsonian Syndromes

The cardinal characteristics of parkinsonism are represented in the mnemonic TRAP: tremor at rest, rigidity, akinesia and bradykinesia, and postural instability. The parkinsonian phenotype encompasses a broad range of clinical and pathologic disorders; the most common (about 55% of cases) is idiopathic (sporadic) Parkinson disease. Rapid disease progression, poor initial response to dopaminergic therapy, or the early presence of certain other signs may suggest an atypical parkinsonian syndrome, sometimes called parkinsonism-plus syndrome.

Neuroinflammatory penumbra in Parkinson’s disease

To date, the etiology and pathogenesis of Parkinson’s disease (PD) are not fully understood. In this publication, we present a critical review of the available international data on the involvement of inflammation processes in the etiopathogenesis of the disease in the context of our research results. The data obtained by us during modeling of parkinsonian syndrome of neuroinflammatory origin (lipopolysaccharide endotoxin was used) in laboratory rats (basic group, n = 21; control group, n = 7) indicate that intranasal administration of lipopolysaccharide in all three studied doses (1, 10 and 100 μg/kg/ml) seven days after the end of the experiment (21 injections) causes the same moderate morphological degenerative and inflammatory changes in the histostructure of the substantia nigra, extending to the striatum area (p > 0.05). This fact can be best explained by the all-or-none law. The staged, sequential transition of primary reversible (neuroinflammatory) pathomorphological changes to secondary irreversible (neurodegenerative) ones in PD, as well as secondary activation of microglia during neuronal degeneration, allows proposing the term “neuroinflammatory penumbra”, which will best help understand the pathogenesis of the disease and the development of therapies that change the course of Parkinson’s disease. Our data on the use of mesenchymal multipotent stromal cells in rats with neurotoxic (rotenone) parkinsonian syndrome (n = 10) and in PD individuals (n = 10) demonstrate a decrease in motor impairment, overall improvement of patients and an effect on laboratory parameters compared with control groups. We associate the early positive effect, observed already in the first week after the administration of mesenchymal multipotent stromal cells, with their paracrine action, including on the neuroinflammatory penumbra.

Parkinsonism secondary to ventriculoperitoneal shunt in a patient with hydrocephalus

Background: Parkinsonism secondary to the treatment of obstructive hydrocephalus due to stenosis of the cerebral aqueduct, with implantation of a ventricular peritoneal (VP) shunt is a rare complication, still poorly described and disseminated in the literature. Case Description: A 38-year-old male presented a history of moderate-intensity daily headache, which deteriorated 2 months before admission, with no changes in the neurological examination. Magnetic resonance imaging showed hypertensive hydrocephalus associated with cerebral aqueduct stenosis. A VP shunt was performed, an adjustable pressure valve was successfully inserted, and he was discharged asymptomatic. However, months later, he progressed with important symptoms of hypo- and hyper-drainage, which persisted after valve pressure adjustments and even its exchange, culminating into an endoscopic third ventriculostomy (ETV). But soon after, severe Parkinsonian syndrome appeared. Therapy with levodopa and bromocriptine was initiated, revealing a slow response initially but good evolution within 6 months. At present, he presents low-intensity residual tremor, which is well controlled with medications, and has regained independence for daily activities, with minimal motor limitation and no cognitive changes. Conclusion: There is still no mechanism that explains the occurrence of Parkinsonian syndrome in these cases. It is suggested that the rostral portion of the midbrain was injured due to abrupt changes in the transtentorial gradient pressure after the ventricular shunt, along with various adjustments in the valve pressure. ETV and early introduction of levodopa therapy in patients who developed postventriculoperitoneal shunt Parkinsonism seems to be the most effective combination, with satisfactory clinical response in the medium/long term.

Clinical utility of DaTscan in patients with suspected Parkinsonian syndrome: a systematic review and meta-analysis

Images of DaTscan (ioflupane [123I] SPECT) have been used as an adjunct to clinical diagnosis to facilitate the differential diagnosis of neurodegenerative (ND) Parkinsonian Syndrome (PS) vs. non-dopamine deficiency aetiologies of Parkinsonism. Despite several systematic reviews having summarised the evidence on diagnostic accuracy, the impact of imaging results on clinical utility has not been systematically assessed. Our objective was to examine the available evidence on the clinical utility of DaTscan imaging in changing diagnosis and subsequent management of patients with suspected PS. We performed a systematic review of published studies of clinical utility from 2000 to 2019 without language restrictions. A meta-analysis of change in diagnosis and management rates reported from each study was performed using a random-effects model and logit transformation. Sub-group analysis, meta-regression and sensitivity analysis was performed to explore heterogeneity. Twenty studies met the inclusion criteria. Thirteen of these contributed to the meta-analyses including 950 and 779 patients with a reported change in management and change in diagnosis, respectively. The use of DaTscan imaging resulted in a change in management in 54% (95% CI: 47–61%) of patients. Change in diagnosis occurred in 31% (95% CI: 22–42%) of patients. The two pooled analyses were characterised by high levels of heterogeneity. Our systematic review and meta-analysis show that imaging with DaTscan was associated with a change in management in approximately half the patients tested and the diagnosis was modified in one third. Regardless of time from symptom onset to scan results, these changes were consistent. Further research focusing on specific patient subgroups could provide additional evidence on the impact on clinical outcomes.

Fahr’s syndrome as a differential diagnosis amid parkinsonian syndromes: a case report

Context: Parkinsonian syndromes are routinely identified by neurologists. However, the differential diagnosis among probable etiologies can be challenging and complex. In Fahr’s syndrome, calcifications of the basal ganglia secondary to disorders of calcium metabolism are observed. A possible clinical presentation associated with this entity is the presence of a parkinsonian syndrome. Case report: A 54-years-old female patient presented with a progressive tremor in the right upper and lower limbs associated with bradykinesia. Seizures were observed during the course of the disease. After extensive clinical workup, primary hypoparathyroidism was diagnosticated along with the recognition of a mutation in the calcium activator gene. Computed tomography and magnetic resonance imaging of the head showed bilateral coarse calcifications in thalami and basal ganglia compatible with Fahr’s syndrome. We began treatment for control of the underlying disease, as well as for symptomatic control of parkinsonism. Conclusions: Different pathologies could justify the parkinsonian syndrome observed initially in the case described. Among them: Iidiopathic Parkinson’s Disease, Multiple System Atrophy, Progressive Supranuclear Palsy. In our patient, the atypical evolution in a young woman led to the research of possible secondary treatable causes. A diagnosis of Fahr’s syndrome related to hypoparathyroidism was unveiled. The differential diagnosis of Parkinson’s Syndrome is broad and difficult. We must be aware of the possible atypical presentations due to the possibility of a secondary condition whose etiology could be effectively treated.

Nanoparticle induced ferroptosis: detection methods, mechanisms and applications

While ferroptosis as an iron-dependent cell death mechanism was involved in the development of some severe diseases (e.g., Parkinsonian syndrome, stroke and tumours), combination of nanotechnology with ferroptosis for the...