TRANSCRANIAL DIRECT CURRENT STIMULATION (t-DCS) AS ADD-ON TO NEUROREHABILITATION OF PISA SYNDROME IN PARKINSON DISEASE
Condition: Parkinson Disease; Pisa Syndrome
MeSH terms: Parkinson Disease; Syndrome
Study type: Interventional

Summary: 
      Pisa Syndrome (PS) is a lateral trunk flexion frequently associated to Parkinson's disease
      (PD). The management of PS is still a challenge for the clinician, because it poorly responds
      to anti-parkinsonian drugs, and the improvement achieved with neurorehabilitation or
      botulinum toxin injections tends to fade in 6 months or less. Transcranial direct current
      stimulation (t-DCS) is a non-invasive neuromodulation technique, with promising results in
      movement disorders. Aim of our study is to evaluate the role of bi-hemispheric t-DCS as
      add-on to neurorehabilitation in PS. Twenty-eight patients affected by PD and PS were managed
      with a 4-week hospital neurorehabilitation programme and randomized to: 1) t-DCS group: 5
      daily sessions (20 minutes - 2 mA) with cathode over the primary motor cortex (M1)
      contralateral to PS, and anode over the M1 cortex ipsilateral to PS; or 2) sham group.
      Patients were tested with kinematic analysis of trunk movement in static and dynamic
      conditions, UPDRS-III, FIM, and VAS for lumbar pain rating at hospital admission (T0), at
      hospital discharge (end of neurorehabilitation - T1), and 6 months later (T2). At T0, the
      evaluations were completed by an EMG study of trunk muscles activation.
    

Detailed description: 
      Axial disorders are frequent complications of Parkinson's Disease (PD) and they can lead to
      postural deformities and balance impairments. The most prevalent postural disorders of PD are
      represented by camptocormia, antecollis, scoliosis, and Pisa syndrome (PS).

      The pathogenesis of these disorders has not yet been completely elucidated, and it is
      characterized by a complex interlacement between central and peripheral mechanisms.

      The first report of PS dates back in 1972, when Ekobm described a case series of three
      patients who developed a lateral trunk flexion in close temporal relationship with
      neuroleptics assumption. The roster of drugs associated with an acute/subacute onset of PS is
      huge and constantly growing, and it includes: antidepressants (mirtazapine, sertraline),
      cholinesterase inhibitor (rivastigmine, galantamine, donepezil), neuroleptics (tiapride,
      clotiapine, clozapine, aipiprazole, butyrophenone, paliperidone, quetiapine), dopamine
      agonists, (pramipexolo, ropinirole, pergolide), lithium, valproic acid, and betahistine.
      Nonetheless, PS was described as well in patients with neurodegenerative disorders, and in
      particular in PD and parkinsonism without drugs exposure.

      The prevalence of PS is around 8.3% (9.3% in women and 6.4% in men) when calculated in a
      psychogeriatric population, and it is 8 to 8.8% when populations of PD patients were
      considered.

      Formal diagnostic criteria for PS are not available, indeed the diagnosis is based on the
      clinical features:

        -  presence of a lateral flexion of the trunk with a homogenous angle between sacrum and
           spinous process of the 7th cervical vertebra;

        -  association of an ipsilateral rotation of the trunk around the sagittal axis that leads
           to a higher and anterior position of the shoulder contralateral to the side of trunk
           deviation;

        -  the postural disorder worsens during standing position, sitting position and gait;

        -  the postural disorder improves in supine position;

        -  disregard of patients for the postural disorder.

      The fluctuation of the postural alteration during static (supine position vs. upright
      standing position) and dynamic conditions appears to be crucial to differentiate PS from
      scoliosis.

      A lateral trunk deviation of at least 10° is commonly accepted for the diagnosis, although
      higher or lower cut-offs were used in the past. According to the degree of the lateral trunk
      flexion, PS can be further divided in mild (less than 20°) or severe (more than 20°)
      phenotypes.

      Patients with PD and PS showed some typical clinical and demographic features when compared
      to PD patients without postural alterations: they are older, PD is longer in duration, more
      severe and with a more pronounced asymmetry of motor symptoms. The parkinsonian symptoms
      involving the upper limbs as well as gait impairment are more severe in PD patients with PS.
      Moreover, they are characterized by a higher incidence of falls, arthrosis, osteoporosis,
      orthopedics diseases and pain, specifically lumbar and lower back pain, which is reported in
      up to 75% of patients with PD and PS.

      The management of PS is still a challenge for the physician. PS poorly responds to
      antiparkinsonian drugs, although there aren't studies specifically designed to assess this
      topic.

      Neurorehabilitation represents one of the fundamental approach to PD and to postural
      disorders in general, not only for the treatment of the motor symptoms itself but also to
      improve quality of life and autonomy in the activity of daily living.

      The study was a randomized, double-blind, controlled trial aimed to assess the efficacy of
      five daily sessions of bi-hemispheric t-DCS in add-on to an in-hospital neurorehabilitation
      protocol in patients affected by PD and PS.

      At hospital admission (T0 - baseline), all patients underwent complete neurological, general
      and functional examinations by a Neurologist with expertise in movement disorders and
      neurorehabilitation. Patients who fulfilled inclusion and exclusion criteria underwent a
      baseline kinematic analysis of trunk movement. Patients with at least 10° of lateral trunk
      flexion completed the baseline evaluations with a dynamic electromyographic (EMG) study of
      trunk muscles, and with administration of a set clinical scales for the evaluations of motor
      disability, functional independence, and lumbar pain.

      After that, patients were randomly assigned to "t-DCS" or "sham" treatment, and they started
      the double-blind phase of the study. The 5-day t-DCS/sham treatment was delivered in 5 daily
      consecutive sessions, starting from the first Monday after hospital admission. In parallel to
      neuromodulation, all patients were treated with a standardized 4-week rehabilitation
      programme. The kinematic analysis of trunk movement as well as the administration of the set
      of questionnaires were repeated at the end of the 4-week rehabilitation programme (T1 -
      hospital discharge), and 6 months after discharge (T2).

      The randomization was performed according to a block randomization method. A unique
      randomization list was generated before enrollment with the following parameters: 6 blocks; 6
      patients per block (3 for t-DCS group, and 3 for sham group).

      All the patients were treated with an optimized and individualized anti-parkinsonian therapy,
      which dose and regimen were kept stable during the overall study period. All the evaluations
      were performed in the morning, and always in an ON phase.

      The specific and standardized in-hospital rehabilitation programme was focused on the
      rehabilitation of the trunk postural disorder. All patients were treated with 90-minute daily
      sessions, 6 days a week (Monday to Saturday) for four weeks.

      Each session was structured as follow:

        -  10 minutes of cardiovascular warm-up activities: intersegmental coordination exercises;
           exercises to release shoulder and pelvic girdle; pelvic anteversion and retroversion
           movements to improve diaphragmatic respiration (supine position); breathing exercises to
           promote expansion of the chest;

        -  15 minutes of stretching exercises: exercises to stretch the muscles of the posterior
           kinematic chain; exercises to stretch the pectoralis muscles; exercises to stretch the
           ischio-cruralis muscles; assumption of the prone position, sitting on heels and
           stretching the arms out in front; the "bridge" exercise to stretch the muscles of the
           anterior abdominal wall, glutei, quadriceps and hamstring; exercises to stretch lumbar
           muscles (in the supine position, each knee, in turn, is brought to the chest);

        -  15 minutes of strengthening exercises in a functional context: exercises to strengthen
           the dorsal muscles (arms extended and hands outstretched as though to take something);
           lateral bending (arms lying along the body and hands reaching down as though to pick up
           something); stretching using the wall bars;

        -  20 minutes of gait training: overground gait training (forwards, backwards, and
           lateral); walking on the spot;

        -  15 minutes of balance training: path with obstacles; balance exercises performed in
           order of difficulty (heel-to-toe walking, lateral walking crossing the legs, walking
           along a path on surfaces of different texture);

        -  15 minutes of relaxation exercises: intersegmental coordination exercises; segmental
           passive mobilization (until maximum joint range of motion is reached); breathing
           exercises to promote expansion of the chest.
    

Intervention name(s): t-DCS group; Sham group
Intervention type(s): Other; Other
Intervention description(s): All the participants received daily stimulation sessions for 5 consecutive days, starting from the first Monday after hospital admission (Monday to Friday). The primary motor cortex (M1) was identified using the International 10-20 system for C3 (left M1) or C4 (right M1). For the stimulation, the anode was placed over the primary motor cortex (M1) ipsilateral to the side of trunk deviation, and the cathode was placed over the primary motor cortex (M1) contralateral to the side of trunk deviation (bi-hemispheric stimulation).; The stimulation setting was exactly the same but the stimulation intensity was set according to a ramping up/ramping down method and delivered only in the first and last 30 seconds of each session. This stimulation paradigm is insufficient to produce a meaningful therapeutic effect, but it is necessary to guarantee the blind condition as it mimics the possible initial tingling sensation associated with active stimulation.
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: The study was a randomized, double-blind, controlled trial
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Parkinson Disease; Pisa Syndrome; Transcranial direct current stimulation