Estimated presence of nonmotor symptoms in <i>LRRK2</i> G2019S Parkinson’s disease patients and idiopathic Parkinson’s disease patients in relation to onset of motor symptoms.

<p><i>LRRK2</i> G2019S PD: <i>LRRK2</i> G2019S related Parkinson’s disease; IPD: Idiopathic Parkinson’s disease, OMS: onset of motor symptoms, RBD: REM sleep behavior disorder, EDS: excessive daytime sleepiness.</p><p>Estimated presence of nonmotor symptoms in <i>LRRK2</i> G2019S Parkinson’s disease patients and idiopathic Parkinson’s disease patients in relation to onset of motor symptoms.</p

University of Pennsylvania Smell Identification Test (UPSIT) scores.

<p>UPSIT scores in LRRK2 G2019S Parkinson’s disease patients, idiopathic Parkinson’s disease patients and healthy controls (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0108982#pone-0108982-g001" target="_blank">Figure 1</a>.A). UPSIT score in each group separated by sex (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0108982#pone-0108982-g001" target="_blank">Figure 1</a>.B). Circles represent individual values, while the bar refers to the mean UPSIT score in each group. IPD: idiopathic Parkinson’s disease; LRRK2-PD: LRRK2 associated Parkinson’s disease, HS: healthy subjects.</p

Nonmotor symptoms in patients with <i>LRRK2</i> G2019S associated Parkinson’s disease, idiopathic Parkinson’s disease and healthy subjects.

<p><i>LRRK2</i> G2019S PD: <i>LRRK2</i> G2019S-related Parkinson’s disease; IPD: Idiopathic Parkinson’s disease; HS: healthy subjects. G-I: Gastro-intestinal; RBD: REM behavior disorder; EDS: excessive daytime sleepiness.</p>#<p>Chi-square test;</p>±<p>Fisher’s exact test;</p>¶<p>Kruskal-Wallis analysis;</p>§<p>Mann-Whitney <i>U</i> test;</p><p>*Statistically significant: <i>P<</i>0.05;</p>1<p>Mean ± Standard deviation (Range);</p>2<p>Hyposmia was arbitrarily defined as an UPSIT score lower than the mean–2 SD UPSIT score obtained in a subset of healthy subjects of the same gender and similar age.</p><p>Nonmotor symptoms in patients with <i>LRRK2</i> G2019S associated Parkinson’s disease, idiopathic Parkinson’s disease and healthy subjects.</p

General demographic data and parkinsonian motor symptoms in patients with <i>LRRK2</i> G2019S associated Parkinson’s disease, idiopathic Parkinson’s disease and healthy subjects.

<p><i>LRRK2</i> G2019S PD: <i>LRRK2</i> G2019S related Parkinson’s disease; IPD: Idiopathic Parkinson’s disease; HS: healthy subjects.</p>1<p>Mean ± Standard deviation (Range).</p>¶<p>Kruskal-Wallis analysis;</p>§<p>Mann-Whitney U test;</p>#<p>Chi-square test;</p>±<p>Fisher’s exact test.</p><p>General demographic data and parkinsonian motor symptoms in patients with <i>LRRK2</i> G2019S associated Parkinson’s disease, idiopathic Parkinson’s disease and healthy subjects.</p

Polysomnography and Multiple Sleep Latency Test data and comparisons between groups.

<p>Data are presented as mean, standard deviation, number and percentage.</p><p>*MSLT was performed in 17 out of 18 LRRK2-PD patients since one refused to undergo this test. Percentages on MSLT measures are therefore based on these 17 subjects.</p><p><b>AHI</b>: Apnea-hipopnea index; <b>LRRK2-PD</b>: LRRK2 Parkinson disease; <b>Mentalis</b>: polysomnographic montage quantifying "any" (phasic and tonic) type of EMG activity in the mentalis muscle during REM sleep, using 3-sec mini-epochs (the cut-off for patients with RBD is 18%)[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0132368#pone.0132368.ref038" target="_blank">38</a>]; <b>Mentalis plus AT</b>: polysomnographic montage quantifying "any" (phasic and tonic) type of EMG activity in the mentalis muscle plus phasic EMG activity in the right and left anterior tibialis during REM sleep, using 3-sec mini-epochs (the cut-off for patients with RBD is 46.4%) [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0132368#pone.0132368.ref038" target="_blank">38</a>]; <b>MSLT</b>: Multiple Sleep Latency Test; <b>NMC</b>: non-manifesting carriers; <b>NMNC</b>: non-manifesting non-carriers; <b>NA</b>: Not applicable; <b>PLMS</b>: Periodic Leg Movements in Sleep; <b>PLMSI</b>: Periodic Leg Movements in Sleep Index; <b>RBD</b>: REM Sleep Behavior Disorder; <b>SINBAR</b>: polysomnographic montage quantifying "any" (phasic or tonic) type of EMG activity in the mentalis muscle and phasic EMG activity in the right and left flexor digitorumsuperficialis muscles during REM sleep, using 3-sec mini-epochs (the cut-off for patients with RBD is 32%)[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0132368#pone.0132368.ref038" target="_blank">38</a>]; <b>SOREMPs</b>: Sleep Onset REM Sleep Periods.</p><p>Polysomnography and Multiple Sleep Latency Test data and comparisons between groups.</p

LRRK2-Parkinson Disease patients with associated REM sleep behavior disorder.

<p><b>LEDD</b>: L-Dopa Equivalent daily dose; <b>M+AT</b>: polysomnographic montage quantifying "any" (tonic or phasic) type of EMG activity in the mentalis muscle plus bilateral anterior tibialis phasic EMG activity in REM sleep, using 3-sec mini-epochs (the cut-off for patients with RBD is 46.4%)[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0132368#pone.0132368.ref038" target="_blank">38</a>]; <b>Mentalis</b>: EMG activity quantification of "any" (tonic and phasic) type of EMG activity in the mentalis muscle during REM sleep, using 3-sec mini-epochs (the cut-off for patients with RBD is 18.2%.)[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0132368#pone.0132368.ref038" target="_blank">38</a>]; <b>MoCA</b>: Montreal Cognitive Assessment; <b>PIGD</b>: postural instability gait difficulty motor subtype; <b>SINBAR</b>: polysomnographyc montage quantifying "any" (tonic or phasic) type of EMG activity in the mentalis muscle and phasic EMG activity in the right and left flexor digitorumsuperficialis muscles during REM sleep, using 3-sec mini-epochs (the cut-off for patients with RBD is 32%)[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0132368#pone.0132368.ref038" target="_blank">38</a>]; <b>RBD</b>: REM sleep behaviour disorder; <b>RBDSQ</b>: REM sleep behavior disorder screening questionnaire; <b>UPDRS-III</b>: Unified Parkinson Disease Rating Scale motor exam; <b>V-PSG:</b> video-polysomnography.</p><p>LRRK2-Parkinson Disease patients with associated REM sleep behavior disorder.</p

Sleep related clinical data and comparisons between groups.

<p>Data are presented as mean, standard deviation, number and percentage.</p><p><b>ESS:</b> Epworth Sleepiness Scale; <b>IPD</b>: Idiopathic Parkinson Disease; <b>IRLSGRS</b>: International Restless Legs Syndrome Study Group Scale; <b>LRRK2-PD</b>: LRRK2 Parkinson Disease; <b>NA</b>: Not applicable; <b>NMC</b>: Non-manifesting carriers; <b>NMNC:</b> Non-manifesting non-carriers; <b>PSQI</b>: Pittsburg Sleep Quality Index; <b>PD</b>: Parkinson disease; <b>PDSS-2</b>: Parkinson’s Disease Sleep Scale 2; <b>RBD</b>: REM sleep behavior disorder; <b>RBDSQ</b>: RBD screening questionnaire.</p><p>Sleep related clinical data and comparisons between groups.</p

Patients with idiopathic Parkinson Disease associated with REM sleep behavior disorder.

<p><b>LEDD:</b> L-Dopa Equivalent daily dose; <b>M+AT</b>: polysomnographic montage quantifying "any" (tonic or phasic) type of EMG activity in the mentalis muscle plus bilateral anterior tibialis phasic EMG activity in REM sleep, using 3-sec mini-epochs (the cut-off for patients with RBD is 46.4%)[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0132368#pone.0132368.ref038" target="_blank">38</a>]; <b>Mentalis</b>: EMG activity quantification of "any" (tonic and phasic) type of EMG activity in the mentalis muscle during REM sleep, using 3-sec mini-epochs (the cut-off for patients with RBD is 18.2%[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0132368#pone.0132368.ref038" target="_blank">38</a>]; <b>MoCA</b>: Montreal Cognitive Assessment; <b>ND</b>: not done; <b>PIGD:</b> postural instability gait difficulty motor subtype; <b>SINBAR</b>: polysomnographyc montage quantifying "any" (tonic or phasic) type of EMG activity in the mentalis muscle and phasic EMG activity in the right and left flexor digitorumsuperficialis muscles during REM sleep, using 3-sec mini-epochs (the cut-off for patients with RBD is 32%[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0132368#pone.0132368.ref038" target="_blank">38</a>]; <b>RBD</b>: REM sleep behaviour disorder; <b>RBDSQ:</b> REM sleep behavior disorder screening questionnaire; <b>TD</b>: tremor dominant motor subtype; <b>UPDRS-III</b>: Unified Parkinson Disease Rating Scale motor exam; <b>V-PSG</b>: video-polysomnography.</p><p>Patients with idiopathic Parkinson Disease associated with REM sleep behavior disorder.</p

Subjects with restless legs syndrome.

<p><b>ESS</b>: Epworth Sleepiness Scale; <b>IRLSGRS</b>: International Restless-legs syndrome Study Group Scale; <b>LEDD</b>: L-Dopa Equivalent daily dose; <b>LRRK2-PD</b>: LRRK2 Parkinson disease subjects;<b>MSLT</b>: Multiple Sleep Latency Sleep Test; <b>NA</b>: Not applicable; <b>NMC</b>: Non-manifesting carriers; <b>NMNC</b>: Non-manifesting non-carriers; <b>PSQI</b>: Pittsburg Sleep Quality Index; <b>PDSS-2</b>: Parkinson Disease Sleep Scale 2; <b>PLMSI</b>: Periodic Leg Movements in Sleep Index; <b>RLS:</b> Restless Legs Syndrome.</p><p>Subjects with restless legs syndrome.</p

Electromyographic activity in REM sleep.

<p>Bars represent the percentage of electromyographic activity found during REM sleep in the different groups included in the study. Grey bars represent the percentage of electromyographic activity found in individuals who were diagnosed with RBD. White bars represent the percentage of electromyographic activity found in individuals who had no RBD. The dotted transversal line indicates that 32% of electromyographic activity is the cut-off value for the diagnosis of RBD according to the SINBAR method. Electromyographic activity ≥32% during REM sleep is indicative of RBD[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0132368#pone.0132368.ref038" target="_blank">38</a>]. IPD: Idiopathic Parkinson disease; LRRK2-PD: LRRK2 Parkinson disease; NMC: non-manifesting carriers; NMNC: non-manifesting non-carriers; RBD: REM sleep behavior disorder; SINBAR: polysomnographic montage quantifying "any" (phasic or tonic) type of EMG activity in the mentalis muscle and phasic EMG activity in the right and left flexor digitorum superficialis muscles during REM sleep using 3-sec mini-epochs.</p