Progressive Micrographia Research Articles

A rare patient with Parkinson's disease presenting with isolated progressive micrographia.

Although handwriting impairment is a frequent sign of Parkinson's disease (PD), its significance in the evaluation processes of these patients may be overlooked among physicians. Therefore, we would like to report an illustrative patient who presented with isolated micrographia initially; but received the diagnosis of PD in the follow-up.

Progressive Micrographia in Trial Writing with a Ballpoint Pen.

Progressive Micrographia in Trial Writing with a Ballpoint Pen.

Diagnostic value of micrographia in Parkinson’s disease: a study with [123I]FP-CIT SPECT

Micrographia is a common symptom of Parkinson’s disease (PD), and it may precede other motor symptoms. Despite the high prevalence of micrographia in PD, its neurobiological mechanisms are not known. Given that levodopa may alleviate consistent micrographia and that nondopaminergic essential tremor (ET) is not associated with micrographia, micrographia could possibly be used as an ancillary diagnostic method that reflects nigrostriatal dopamine function. We evaluated the usefulness of micrographia as a simple one-sentence writing test in differentiating PD from ET. A total of 146 PD patients, 42 ET patients and 38 healthy controls provided writing samples and were scanned with brain [123I]FP-CIT dopamine transporter (DAT) SPECT imaging with ROI-based and voxelwise analyses. The diagnostic accuracy of micrographia was evaluated and compared to that of DAT binding. Compared to ET and healthy controls, PD patients showed micrographia (consistent, 25.6% smaller area of handwriting sample in PD compared to ET, p = 0.002, and 27.2% smaller area of handwriting compared to healthy controls, p = 0.004). PD patients showed 133% more severe progressive micrographia compared with ET patients (median b = − 0.14 in PD, b = − 0.06 in ET, p = 0.021). In early unmedicated cognitively normal patients, consistent micrographia showed 71.2% specificity and 87.5% sensitivity in PD versus ET differentiation, but micrographia had no correlation with striatal or extrastriatal [123I]FP-CIT binding in patients with PD. The one-sentence micrographia test shows moderately good accuracy in PD versus ET differentiation. The severity of micrographia has no relationship with DAT binding, suggesting nondopaminergic mechanism of micrographia in PD.ClinicalTrials.gov identifier: NCT02650843 (NMDAT study).

Differences in Levodopa Response for Progressive and Non-Progressive Micrographia in Parkinson's Disease.

Background: Micrographia, one element of the dysgraphia of Parkinson's disease (PD), may be classified according to the presence or absence of a decremental pattern. The decremental form, progressive micrographia, is an expression of the sequence effect seen generally in bradykinesia. Its responsiveness to levodopa has not been evaluated kinematically.Objectives: Aim of this study is to investigate the difference in levodopa response for progressive and non-progressive micrographia.Methods: Twenty-four PD patients and 24 age-matched repeatedly wrote the letter e on a computerized digital tablet. PD patients performed the task two times, in a defined off state and again after levodopa. Scripts were classified as progressive micrographia (PDPM) or non-progressive micrographia (PDNPM) depending on whether a 10% decrement was seen between the first and final characters of a line of lettering.Results: While levodopa produced a similar response on the MDS-UPDRS motor scale for the two groups, the effect on the two types of micrographia was different. While writing speed improved significantly in both groups after levodopa, the responses were over twofold greater for PDNPM. Moreover, the decremental features of PDPM–in size, speed, and pen-pressure—were largely unaltered by a levodopa dose.Conclusions: Progressive micrographia is less responsive to levodopa. Our findings agree with research showing that the sequence effect of bradykinesia is relatively resistant to medication. Yet we did not find a weaker overall levodopa motor benefit. Caution is needed in the interpretation of such micrographia measurements for estimating drug responses.

Neural substrates underlying progressive micrographia in Parkinson's disease.

IntroductionThe neural substrates associated with the development of micrographia remain unknown. We aimed to elucidate the neural substrates underlying micrographia in Parkinson's disease (PD) patients.MethodsForty PD patients and 20 healthy controls underwent handwriting tests that involved free writing and copying. We measured the size of each letter and the resting cerebral glucose metabolic rate of the PD patients and another group of age‐ and sex‐matched 14 healthy controls (HCs), who had not participated in the writing tests, using resting‐state 18F‐fluorodeoxyglucose positron emission tomography.ResultsIn the PD patients, the prevalence of consistent micrographia (CM) associated with free writing was 2.5% for both tasks. Alternatively, the prevalence of progressive micrographia (PM) was 15% for free writing and 17.5% for copying. In the PD patients, there was no significant difference in the letter sizes between these tasks, whereas the variability of the letter sizes for copying was significantly different from that for free writing. The means and decrements in letter sizes in either task were not significantly correlated with the severity of brady/hypokinesia in the PD patients. For free writing, the PD patients with PM showed glucose hypometabolism in the anterior part of the right middle cingulate cortex, including the rostral cingulate motor area, compared with those without PM. For copying, the PD patients with PM showed glucose hypometabolism in the right superior occipital gyrus, including V3A, compared with those without PM.ConclusionsThese findings suggest that PM in free writing in PD patients is caused by the difficulty of monitoring whether the actual handwriting movements are desirable for maintaining letter size during self‐paced handwriting. By contrast, PM in copying in PD patients is evoked by a lack of visual information about the personal handwriting and hand motions that are used as cues for maintaining letter sizes.

A Kinematic Study of Progressive Micrographia in Parkinson's Disease.

Progressive micrographia is decrement in character size during writing and is commonly associated with Parkinson's disease (PD). This study has investigated the kinematic features of progressive micrographia during a repetitive writing task. Twenty-four PD patients with duration since diagnosis of <10 years and 24 age-matched controls wrote the letter “e” repeatedly. PD patients were studied in defined off states, with scoring of motor function on the Unified Parkinson's Disease Rating Scale Part III. A digital tablet captured x-y coordinates and ink-pen pressure. Customized software recorded the data and offline analysis derived the kinematic features of pen-tip movement. The average size of the first and the last five letters were compared, with progressive micrographia defined as >10% decrement in letter stroke length. The relationships between dimensional and kinematic features for the control subjects and for PD patients with and without progressive micrographia were studied. Differences between the initial and last letter repetitions within each group were assessed by Wilcoxon signed-rank test, and the Kruskal-Wallis test was applied to compare the three groups. There are five main conclusions from our findings: (i) 66% of PD patients who participated in this study exhibited progressive micrographia; (ii) handwriting kinematic features for all PD patients was significantly lower than controls (p < 0.05); (iii) patients with progressive micrographia lose the normal augmentation of writing speed and acceleration in the x axis with left-to-right writing and show decrement of pen-tip pressure (p = 0.034); (iv) kinematic and pen-tip pressure profiles suggest that progressive micrographia in PD reflects poorly sustained net force; and (v) although progressive micrographia resembles the sequence effect of general bradykinesia, we did not find a significant correlation with overall motor disability, nor with the aggregate UPDRS-III bradykinesia scores for the dominant arm.

Acute Deep Venous Thrombosis Unmasking Underlying Wilson’s Disease: Case Report

Introduction: Wilson’s disease (WD), also known as hepato-lenticular disease, is an autosomal recessive disorder of copper excretion and can clinically present with hepatic, neurological, and psychiatric manifestations, which makes the diagnosis challenging in most of the cases. We present a case whose atypical presentation led to the unmasking of his underlying WD. Case Report: A 32-year-old male, recently diagnosed with type II diabetes mellitus, presented with pain and swelling of right lower extremity. On detailed history, the patient mentioned having a 3-month history of intention tremors, sialorrhea, hypophonia, progressive micrographia, and family history of a second-degree relative having WD. He had advanced intension tremors, cogwheel rigidity in the upper extremities, and olfactory dysfunction. His laboratory investigations showed D-dimer of 4,335 units, elevated PT (16.5 sec) and INR (1.8), and low albumin level (3.0 gm/dl) with normal liver enzymes. Right popliteal acute deep venous thrombosis (DVT) was confirmed by Doppler US. MRI brain showed cortical and cerebellar atrophy. MRI abdomen showed liver cirrhosis, mild splenomegaly, and small esophageal varices. Extensive work-up proved the diagnosis of WD by low serum copper level of 60 mcg/dL, low serum ceruloplasmin level of 15 mg/dL, and high 24-hour urine copper of 211 mcg. Liver biopsy showed macrovascular steatosis less than 5%, grade 3 portal and periportal chronic inflammation, grade 1-2 lobular inflammation, and stage 2 portal fibrosis with intact architecture and negative iron stain. Chemical quantification of copper in the liver biopsy was 219 ug/g drywt. Discussion: WD is caused by mutation of ATP7B gene on long arm of chromosome 13, which codes for a protein responsible for incorporating excess copper into ceruloplasmin to be excreted from the body. Subsequently, this leads to accumulation of copper in several organs, mainly the liver, brain, and cornea, and inevitably leads to progressive liver and neurological dysfunction. Hepatic manifestations range from asymptomatic biochemical abnormalities to acute hepatitis or chronic hepatitis and cirrhosis. Neurological manifestations include dysarthria, dystonia, tremors, or Parkinson’s-like manifestations. Less commonly, WD may present with cerebellar manifestations. Our patient had manifestations of cerebellar involvement as well as Parkinsonian features. This case presents a unique initial presentation of WD in the form of unprovoked DVT secondary to the hypercoagulable state, complicating chronic liver disease. As far as we know, DVT has not been reported to be one of the presenting complications of WD especially in patients without advanced liver cirrhosis.

Progressive Micrographia Shown in Horizontal, but not Vertical, Writing in Parkinson’s Disease

All published studies on micrographia, a diminution of letter size, examine handwriting in the horizontal direction. Writing horizontally typically requires increased wrist extension as handwriting progresses from left to right. Chinese characters, however, can be written not only horizontally from left to right, but also vertically from top to bottom. We examined the effect of handwriting direction on character size and stroke length. Fifteen participants with Parkinson’s disease (PD) and 15 age-matched controls wrote the same Chinese characters both horizontally and vertically. Handwriting performance was recorded with a digitizing tablet, and a custom-written computer program was used to provide objective data about character size and stroke length. The PD group had a linear decrease in overall character size and horizontal strokes along the writing sequence in the horizontal direction, but not in the vertical direction. The controls had shorter horizontal strokes in the horizontal than the vertical direction, but there was no progressive shortening of stroke length along the writing sequence. The results suggest that traditionally reported progressive micrographia in horizontal writing may not be generalizable to vertical writing. The observed decrease of handwriting size in the horizontal direction suggests that micrographia in PD may be associated with wrist extension. For clinical implications, patients may mitigate their micrographia by changing handwriting direction.

Progressive micrographia shown in horizontal, but not vertical, writing in Parkinson's disease.

All published studies on micrographia, a diminution of letter size, examine handwriting in the horizontal direction. Writing horizontally typically requires increased wrist extension as handwriting progresses from left to right. Chinese characters, however, can be written not only horizontally from left to right, but also vertically from top to bottom. We examined the effect of handwriting direction on character size and stroke length. Fifteen participants with Parkinson’s disease (PD) and 15 age-matched controls wrote the same Chinese characters both horizontally and vertically. Handwriting performance was recorded with a digitizing tablet, and a custom-written computer program was used to provide objective data about character size and stroke length. The PD group had a linear decrease in overall character size and horizontal strokes along the writing sequence in the horizontal direction, but not in the vertical direction. The controls had shorter horizontal strokes in the horizontal than the vertical direction, but there was no progressive shortening of stroke length along the writing sequence. The results suggest that traditionally reported progressive micrographia in horizontal writing may not be generalizable to vertical writing. The observed decrease of handwriting size in the horizontal direction suggests that micrographia in PD may be associated with wrist extension. For clinical implications, patients may mitigate their micrographia by changing handwriting direction.

104 Accuracy of objective handwriting assessment for differentiating Parkinson's disease from tremulous Subjects Without Evidence of Dopaminergic Deficits (SWEDDs): an FP-CIT validated study

Handwriting is commonly performed in the clinical analysis of tremor and Parkinson's disease (PD). In this study we analysed the accuracy of objective measurement of handwriting samples for distinguishing 27...

On the genesis of unilateral micrographia of the progressive type

We report a patient who, following a focal ischemic lesion of the left basal ganglia, developed right hand micrographia characterised by progressive reduction of letter size during writing (progressive micrographia). The patient did not show relevant cognitive impairments, but achieved pathological scores in tests for verbal fluency, and cognitive flexibility and monitoring. A systematic investigation of the writing performances demonstrated that micrographia showed a clear length effect in whatever writing style or task, while it was not observed in drawing, or in left hand writing to a comparable extent. Right hand progressive micrographia was not affected by a concurrent motor and cognitive load; instead, switching between two kinds of allographic responses and presenting one letter at a time in copying tasks reduced severity of micrographia significantly. These findings support the view that progressive micrographia in our patient could be ascribed to a defect in regulating the motor output on the basis of self-generated strategies. This conclusion would be consistent with neuroimaging evidence about the role of the basal ganglia in the control of motor sequencing, and could suggest that progressive micrographia might be associated with specific executive defects.

Micrographia on free writing versus copying tasks in idiopathic Parkinson's disease

Background Only a few studies have reported on the frequency of micrographia in idiopathic Parkinson's disease (IPD), and the definition of micrographia in these studies was based simply on the visual inspection of the patients' free writing. Objectives We investigated the frequency of consistent (CM) and progressive (PM) micrographia by quantifying the patients' copying of a target letter or figure. Methods Seventy-five IPD patients and 30 sex/age matched healthy controls were assigned the tasks of free writing and letter/figure copying. CM was defined by the average size of the letter or figure written or copied by the patients below the controls' mean−2SD. PM was defined by the slope of reduction in size as a function of the serial positioning of the letters/figures below the mean−2SD of the controls. Results In the free writing, of 75 patients, only one met the criteria for the definition of CM and two met the criteria for the definition of PM definition. In contrast, letter/figure copying tasks identified 33 (44%) patients with CM and 19 (25%) with PM. Conclusion Our study suggests that the prior definition of CM or PM by visual inspection in free writing task is less valid, and that the definition of CM and PM, based on the letter/figure copying tasks rather than free writing tests, could be more objective.