24 July 2021
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Original Citation:
Awareness of Symptoms Amelioration Following Low-frequency Repetitive Transcranial Magnetic Stimulation in a
Patient With Tourette Syndrome and Comorbid Obsessive-compulsive Disorder
Published version:
DOI:10.1016/j.brs.2014.01.002
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10.1016/j.brs.2014.01.002.
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Awareness o f Symptoms Am elioration
Follow ing Low-frequency Repetitive
Transcranial M agnetic Stimulation in a
Patient W ith Tourette Syndrome and
Comorbid Obsessive-compulsive
Disorder
Dear Editor:
W e report the follo w in g case to highlight the im portance o f keeping into account the patient’s awareness o f the disease in studies investigating the efficacy o f repetitive transcranial m agnetic stimulation (rTM S) treatm ent in patients w ith Tourette Syndrome (TS) and com orbid obsessive-com pulsive disorder (OCD). Reduction o f tic severity has been shown follo w in g low -frequency rTMS over Supplem entary M otor Area (SM A) in TS patients w ith or w ith out co m orbid OCD [1—3]. SMA represents an ideal target for rTMS in these patients, considering that it is richly connected w ith cortical and subcortical regions involved both in m otor control and in TS patho physiology [2]. Indeed, this site activity correlates w ith tic produc tion in TS [4]. Furthermore, SMA is hyperactive in OCD patients [5]. W e report the case o f a 49-year-old right-handed man (13 years o f education ) w ith severe TS and com orbid OCD w h o was referred for rTMS treatm en t by his neurologist. W h e n the patient was first diagnosed, at the age o f 14, he m anifested severe m otor and vocal tics w ith strident screams accom panied by v io le n t self-injurious behaviors. At the tim e o f th e study, his m otor and vocal tics w e re partially con trolled by m edications — sertraline (150 mg/d), aripiprazole (10 mg/d), clon azepam (4 mg/d), haloper- idol (1 mg/d) w ith biperiden (2 mg/d), delorazep am (1 mg/d, as n eed ed ) and tram adol (5 0 —100 mg/d, as n eed ed ) — w ith the exception o f self-injurious behaviors and screams that occurred at least once a day.
The patient signed a w ritten inform ed consent to participate to the study, w hich was approved by the Local Ethical Committee. Medications w e re continued throughout the study. Functional and
Table 1
C lin ica l m e a s u re s ( A ) a n d a d - h o c q u e s tio n n a ir e (B ) sc o re s c o lle c t e d th e w e e k b e fo r e (P r e ) a n d th e w e e k a ft e r (P o s t ) t w o rT M S a p p lic a tio n s . Pre P o s t A . YG TSS M O V E S BDI BAI Q O L -A D N u m b e r o f crises M e a n d a ily fr e q u e n c y M e a n in te n s ity ^ M e a n in te rfe re n c e ^ 85 12 2 14 23 7 1 2.1/5 2/5 70 3 2 9 18 4
0.6
1.4/5 0.8/5 A . T o ta l t ic s c o re fo r th e Y a le - G lo b a l T ic S e v e r it y S cale (Y G T S S ); M o t o r tic, O b sessio n s an d c o m p u ls io n s , V o c a l tic E v a lu a tio n S u r v e y (M O V E S ); B eck D e p r e s s io n In v e n t o r y (B D I); B e c k A n x ie t y I n v e n t o r y (B A I); Q u a lity o f L ife in A D (Q O L -A D ).B. R esu lts o f th e a d - h o c q u e s tio n n a ir e o n w e e k l y s e lf-in ju r io u s b e h a v io rs .
‘ In te n s ity a n d in t e r fe r e n c e w e r e s c o re d o n a 0 to 5 p o in ts scale (0 = m in im u m in te n s ity / in te r fe r e n c e ; 5 = m a x im u m in te n s ity / in te r fe r e n c e ).
neuropsychiatric evaluations com prised the Yale-Global Tic Severity Scale (YGTSS), M otor tic Obsessions and compulsions Vocal tic Eval uation Survey (MOVES), Beck Depression Inventory (BDI), Beck A n x iety Inventory (BAI) and the Quality o f Life in AD (QOL-AD). The patient underw ent these evaluations at the end o f the w eek preced ing the w eek o f treatm ent and after one w e ek from the last stimu lation. The frequency o f w eek ly self-injurious behaviors, their intensity and interference on everyday activities w ere quantified us ing an ad-hoc questionnaire that was com pleted by the patient, on a daily basis, during the w e ek that preceded and the w eek that fol low ed rTMS. Before starting the treatment, the patient was w orried about having to com e every day to the hospital, given his poor con trol over TS symptoms. RTMS was adm inistered at 1 Hz over pre- SMA [ 1,6] using a 70 m m figu re-of-eight coil and the MagStim Super Rapid stimulator (M agstim Company Ltd., W hitland, UK). EMG m onitoring was perform ed from the right EDI muscle. The intensity o f stimulation was set at 80% o f resting M otor Threshold. A t the end o f stimulation the patient was m onitored for 30 min. On the first day, he received three trains o f 5 min w ith inter-train intervals o f 2 m in (900 stimuli). On the second day, he received six trains o f 3 m in and one train o f 2 min w ith inter-train intervals o f 2 min (1200 stimuli). Although the treatm ent was supposed to include 10 daily sessions, after the second session the patient dropped out. He called reporting he had an “epileptic seizure” after 40 min from rTMS and others seizures after about an hour. However, the pa tient’s description o f the even t (self-injurious behaviors w ith screaming and crying), his responses about specific sym ptom s (no loss o f consciousness, no postictal confusion, no urinary or fecal in continence, no tongue biting), and the normal EMG led the neurol ogist to exclude that w h at occurred w ere real seizures. They rather appeared to be hysteric or m ore intense self-injurious crises. The pa tient preferred not to com e to the hospital to undergo EEG or other exams the same day. H owever, he was w illin g to com plete the sec ond part o f the study and to com e back after one w eek to undergo the post-treatm ent assessment. The day after, one o f us brought the ad-hoc questionnaire to his home.
The w e e k subsequent to the rTMS sessions, the patient showed 18% am elioration on the YGTSS, 75% im provem en t on the MOVES, 36% im provem en t on the BAI, and a reduction o f the number, in tensity and interference w ith daily life activities o f the crises. On the oth er hand, 22% decrease was found on the QOL-AD score, indexing a w o rsen in g o f the subjectively p erceived quality o f life (see Table 1). Alth ough som e degree o f variance in reportin g sym ptom s at th e tw o tim e points cannot be totally ruled out, the patient’s concern about perform in g accurately his tasks and
the coh erence in reportin g a reduction o f sym ptom s across tests in the post-treatm ent evaluation seem to support a certain reliability.
Discussion
This case-report shows im provem en t o f TS sym ptom s follo w in g rTMS over SMA [1—3]. It also suggests a dissociation b etw een the clinical condition and the awareness o f sym ptom s am elioration. Although sym ptom s evaluation on the assessment scales was based on the patient’s description o f items and events, he seem ed to be not aware o f the im provem en t as he overtly reported no benefits and w orsenin g o f quality o f life after treatment. Conversely, w e m ay suggest that follo w in g rTMS he actually im proved his aw are ness for the disease.
Inhibition o f SMA m ight have reduced the urge to act [7] and TS symptoms. Yet, m odulation o f SMA m ight have affected other pre m otor areas belonging to the neural circuit underlying m otor awareness [8], consequently im provin g the patient’s awareness o f the disease. Although the presence o f anosognosia was not evalu ated b efore treatment, the patient’s high scores on quality o f life assessment suggest sym ptom s underestim ation and poor insight. M oreover, com orbidity w ith OCD m ay have reduced the patient’s awareness o f the disease [9]. On the other hand, rTMS-induced im provem en t o f awareness m ight have (paradoxically) decreased the patient com pliance w ith the treatment. Indeed, dropouts o f TS patients w ith com orbid OCD from rTMS treatm ent have been previously reported [1].
Future double-blind placebo-controlled studies on groups o f patients are needed to b etter understand the effectiveness o f rTMS over SMA for the treatm en t o f TS and the im pact that com orbid OCD and anosognosia m ay exert on the patients’ com pliance.
Adriana Salatino, Elisabetta M om o
M arcello Nobili
Annamaria Berti, Raffaella Ricci»
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