Freezing of gait: A rare delayed complication of whole brain radiation

Hatcher-Martin, Jaime M.; Factor, Stewart A.

doi:10.1016/j.parkreldis.2016.05.002

Cited by 5 publications

(5 citation statements)

References 5 publications

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“…There are also studies extant linking impaired neurovascular coupling to gait dysfunction in the elderly (Sorond et al 2011). Thus, we speculate that WBIinduced neurovascular coupling may also contribute to the gait/motor coordination abnormalities observed in our present study as well as in previous reports (Brown et al 2016;Hatcher-Martin and Factor 2016). Further studies are warranted to determine whether changes in gait after WBI correlate with the severity of post-radiation cerebromicrovascular deficits.…”

Section: Discussionsupporting

confidence: 66%

“…The available experimental data clearly demonstrate that radiation also leads to a progressive impairment of cognitive function in animal models, mimicking the clinical scenario of cognitive decline in patients after WBI (Lamproglou et al 2001;Shi et al 2006;Soussain et al 2009;Warrington et al 2012;Welzel et al 2008aWelzel et al , 2008b. Recent studies show that in addition to its profound harmful effects on cognitive function, WBI can also result in the impairment of other brain functions such as coordination of gait (Hatcher-Martin and Factor 2016). At present, no effective strategies exist to prevent radiation-induced decline in higher brain functions and there are no treatments available to reverse these effects.…”

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confidence: 89%

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Cerebromicrovascular dysfunction predicts cognitive decline and gait abnormalities in a mouse model of whole brain irradiation-induced accelerated brain senescence

et al. 2017

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Whole brain irradiation (WBI) is a mainstream therapy for patients with both identifiable brain metastases and prophylaxis for microscopic malignancies. However, it also promotes accelerated senescence in healthy tissues and leads to progressive cognitive dysfunction in up to 50% of tumor patients surviving long term after treatment, due to γ-irradiation-induced cerebromicrovascular injury. Moment-to-moment adjustment of cerebral blood flow ( C B F ) v i a n e u r o n a l a c t i v i t y -d e p e n d e n t cerebromicrovascular dilation (functional hyperemia) has a critical role in maintenance of healthy cognitive function. To determine whether cognitive decline induced by WBI associates with impaired cerebromicrovascular function, C56BL/6 mice (3 months) subjected to a clinically relevant protocol of fractionated WBI (5 Gy twice weekly for 4 weeks) and control mice were compared. Mice were tested for spatial memory performance (radial arm water maze), sensorimotor coordination (computerized gait analysis, CatWalk), and cerebromicrovascular function (whisker-stimulation-induced increases in CBF, measured by laser Doppler flowmetry) at 3 to 6 months post-irradiation. We found that mice with WBI exhibited impaired cerebromicrovascular function at 3 months post-irradiation, which was associated with impaired performance in the radial arm water maze. At 6 months, post-irradiation progressive impairment in gait coordination (including changes in the regularity index and phase dispersion) was also evident. Collectively, our findings provide evidence for early and persisting neurovascular impairment after a clinically relevant protocol of fractionated WBI, which predict early manifestations of cognitive impairment.

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Section: Discussionsupporting

confidence: 66%

mentioning

confidence: 89%

Cerebromicrovascular dysfunction predicts cognitive decline and gait abnormalities in a mouse model of whole brain irradiation-induced accelerated brain senescence

et al. 2017

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“…Still, the mechanisms remain unclear. Eye movement recordings have been reported as reflections of tenuous cognitive deficits before their clinical manifestation (10). Oculomotor and balance functions are also closely interwoven.…”

Section: Introductionmentioning

confidence: 99%

Balance Impairment in Radiation Induced Leukoencephalopathy Patients Is Coupled With Altered Visual Attention in Natural Tasks

et al. 2019

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Background: Recent studies have shown that alterations in executive function and attention lead to balance control disturbances. One way of exploring the allocation of attention is to record eye movements. Most experimental data come from a free viewing of static scenes but additional information can be leveraged by recording eye movements during natural tasks. Here, we aimed to provide evidence of a correlation between impaired visual alteration in natural tasks and postural control in patients suffering from Radiation-Induced Leukoencephalopathy (RIL).Methods: The study subjects were nine healthy controls and 10 patients who were diagnosed with RIL at an early stage, with isolated dysexecutive syndrome without clinically detectable gait or posture impairment. We performed a balance evaluation and eye movement recording during an ecological task (reading a recipe while cooking). We calculated a postural score and oculomotor parameters already proposed in the literature. We performed a variable selection using an out-of-bag random permutation and a random forest regression algorithm to find: (i) if visual parameters can predict postural deficit and, (ii) which are the most important of them in this prediction. Results were validated using the leave-one-out cross-validation procedure.Results: Postural scores indeed were found significantly lower in patients with RIL than in healthy controls. Visual parameters were found able to predict the postural score of RIL patients with normalized root mean square error (RMSE) of 0.16. The present analysis showed that horizontal and vertical eye movements, as well as the average duration of the saccades and fixations influenced significantly the prediction of the postural score in RIL patients. While two patients with very low MATTIS-Attention sub score showed the lowest postural scores, no statistically significant relationship was found between the two outcomes.Conclusion: These results highlight the significant relationship between the severity of balance deficits and the visual characteristics in RIL patients. It seems that increased balance impairment is coupled with a reduced focusing capacity in ecological tasks. Balance and eye movement recordings during a natural task could be a useful aspect of multidimensional scoring of the dysexecutive syndrome.

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“…A literature review on secondary parkinsonism caused by radiation treatment to the brain revealed six cases reported in the literature, including two pediatric and four adult patients [ 8 - 14 ]. These patients did not significantly respond to levodopa therapy, presumably due to alternate mechanisms of injury.…”

Section: Discussionmentioning

confidence: 99%

“…The patient progressively deteriorated and deceased within one year of evaluation at the movement disorder clinic. One patient developed secondary Parkinson's syndrome during radiation treatment, while another patient developed symptoms seven years after treatment, and the fourth patient developed symptoms 39 years after radiation treatment [ 8 , 12 - 14 ]. All these patients were resistant to carbidopa-levodopa treatment for the resolution of their symptoms.…”

Section: Discussionmentioning

confidence: 99%