Sarah Herremans

Intensive HF-rTMS treatment in refractory medication-resistant unipolar depressed patients.

BACKGROUND Major depression is a worldwide severe mental health problem. Unfortunately, not all depressed patients respond to pharmacotherapy or psychotherapy, even when adhering to treatment guidelines. Even though current guidelines do not in particular advocate repetitive Transcranial Magnetic Stimulation (rTMS) in refractory treatment resistant depression (TRD), using more intensive stimulation parameters might hold promise as a valuable alternative. OBJECTIVE Consequently, in this randomized sham-controlled crossover study, we wanted to evaluate clinical outcome of intensive HF-rTMS treatment in TRD when applied to the left dorsolateral prefrontal cortex (DLPFC). METHODS After a 2-week antidepressant washout, 20 unipolar TRD patients, at least stage III, received 20 sham-controlled high-frequency (HF)-rTMS sessions, in a crossover design. Five daily suprathreshold HF-rTMS sessions were spread over four successive days delivering in total 31,200 stimuli. RESULTS Overall, the procedure resulted in immediate statistical significant decreases in depressive symptoms regardless of order/type of stimulation (real/sham), suggesting possible placebo responses. On the other hand, albeit only 35% (7/20) of the patients showed a 50% reduction of their initial Hamilton Depression rating score at the end of the two-week procedure, all these patients showed a prompt clinical response after real HF-rTMS treatment, not after sham. Furthermore, a shorter duration of the current depressive episode was a predictor for beneficial clinical outcome. Unresponsiveness to former ECT could be indicative for negative clinical outcome in these kinds of patients. LIMITATIONS Single center setup with relatively small sample size and no follow-up. CONCLUSIONS Our findings indicate that intensive HF-rTMS treatment might have the potential to result in fast clinical response when confronted with a refractory TRD patient.

The Impact of Accelerated Right Prefrontal High-Frequency Repetitive Transcranial Magnetic Stimulation (rTMS) on Cue-Reactivity: An fMRI Study on Craving in Recently Detoxified Alcohol-Dependent Patients

In alcohol-dependent patients craving is a difficult-to-treat phenomenon. It has been suggested that high-frequency (HF) repetitive transcranial magnetic stimulation (rTMS) may have beneficial effects. However, exactly how this application exerts its effect on the underlying craving neurocircuit is currently unclear. In an effort to induce alcohol craving and to maximize detection of HF-rTMS effects to cue-induced alcohol craving, patients were exposed to a block and event-related alcohol cue-reactivity paradigm while being scanned with fMRI. Hence, we assessed the effect of right dorsolateral prefrontal cortex (DLPFC) stimulation on cue-induced and general alcohol craving, and the related craving neurocircuit. Twenty-six recently detoxified alcohol-dependent patients were included. First, we evaluated the impact of one sham-controlled stimulation session. Second, we examined the effect of accelerated right DLPFC HF-rTMS treatment: here patients received 15 sessions in an open label accelerated design, spread over 4 consecutive days. General craving significantly decreased after 15 active HF-rTMS sessions. However, cue-induced alcohol craving was not altered. Our brain imaging results did not show that the cue-exposure affected the underlying craving neurocircuit after both one and fifteen active HF-rTMS sessions. Yet, brain activation changes after one and 15 HF-rTMS sessions, respectively, were observed in regions associated with the extended reward system and the default mode network, but only during the presentation of the event-related paradigm. Our findings indicate that accelerated HF-rTMS applied to the right DLPFC does not manifestly affect the craving neurocircuit during an alcohol-related cue-exposure, but instead it may influence the attentional network.

Pseudomalabsorption of Levothyroxine: A Challenge for the Endocrinologist in the Treatment of Hypothyroidism

Background: Hypothyroidism due to non-compliance with levothyroxine therapy (pseudomalabsorption) is rare. The diagnosis is considered in patients with persistent severe hypothyroidism despite treatment with large doses of levothyroxine. Intestinal malabsorption, drug and dietary interference with levothyroxine absorption and nephrotic syndrome should be excluded. The diagnosis of pseudomalabsorption can be demonstrated by using “an oral 1,000 µg of levothyroxine test” showing a rapid decrease in thyroid-stimulating hormone and increase in thyroxine. There are however few data on the sensitivity and specificity of the test in large cohorts of hypothyroid patients. Treatment of pseudomalabsorption is controversial, with reports using parenteral, intramuscular or single weekly oral dosing of levothyroxine. Cases: We report 3 patients who presented with persistent clinical and biochemical signs of hypothyroidism despite replacement therapy with high doses of levothyroxine. Pseudomalabsorption was diagnosed by a systematic approach, including prior exclusion of digestive, liver and kidney diseases. A peroral challenge test was positive in all cases. Patients denied non-compliance, and a psychiatric approach was elusive. Two of the patients were treated successfully with a single supervised weekly 1,000-µg administration of levothyroxine, while non-supervised weekly administration resulted in hypothyroidism confirming pseudomalabsorption. Conclusions: Non-compliance with medical therapy should be considered in patients with treatment-refractory hypothyroidism. Supervised once weekly levothyroxine treatment is a safe and well-tolerated treatment option, obviating the need for parenteral administration of the drug. Apart from the medical treatment, there is also a need for psychiatric evaluation and care.

Accelerated repetitive transcranial magnetic stimulation does not influence grey matter volumes in regions related to alcohol relapse: An open-label exploratory study

The application of repetitive transcranial magnetic stimulation (rTMS) to prevent relapse in alcohol addiction is currently being evaluated. However, how rTMS may influence the related brain processes is far from clear. Here we wanted to investigate whether baseline grey matter volume (GMV) can predict relapse and whether 15 accelerated high-frequency (HF)- rTMS sessions may influence GMV in areas related to relapse. Voxel-based morphometric (VBM) measurements were used to compare baseline GMV of 22 detoxified, hospitalized, alcohol-dependent patients with 22 age and gender matched healthy control subjects. Only patients received 15 accelerated HF-rTMS sessions at the right dorsolateral prefrontal cortex (DLPFC) followed by VBM measurements. Relapse rates were assessed four weeks after the end of the stimulation protocol. At baseline, alcohol-dependent patients overall showed less GMV in diffuse brain areas compared to healthy controls. Relapsers compared to abstainers displayed larger GMV decreases, especially in brain midline structures, insular, hippocampal, and amygdalar areas. Accelerated HF-rTMS treatment had no significant effect on GMV in alcohol-dependent patients, regardless of the relapse state. Although an accelerated HF-rTMS treatment protocol did not influence GMV in alcohol-dependent patients, baseline GMV predicted future relapse.

Diepe hersenstimulatie bij verslaving

Afhankelijkheid van psychoactieve middelen is een moeilijk te behandelen aandoening. Het terugvalpercentage is dan ook erg hoog. Deze psychiatrische conditie heeft een belangrijke impact op de lichamelijke gezondheid en het sociaaleconomisch functioneren van patienten en gaat gepaard met cognitieve tekorten. In het ontstaan en de evolutie van verslaving speelt het beloningssysteem een cruciale rol. De huidige beschikbare therapeutische mogelijkheden lijken evenwel onvoldoende. Vanwege het modulerend effect in neuronale circuits zou diepe hersenstimulatie (‘deep brain stimulation’, DBS) een gunstig effect op therapieresistente afhankelijkheid kunnen hebben. Verder onderzoek naar effectiviteit, werkingsmechanisme en stimulatieparameters is echter noodzakelijk. Richtlijnen dienen uitgewerkt te worden.

EPA-0925 - The application of neuromodulation techniques in the treatment of alcohol addiction

Only a limited number of alcohol dependent patients appear to benefit from existing psychotherapeutic and pharmacological treatment modalities. This fact highlights the need for different treatment approaches. Recent evidence however, suggests a possible beneficial role for neuromodulation techniques. In particular, repetitive transcranial magnetic stimulation (rTMS) seems able to change subjective alcohol craving, an important factor in relapse risk. Further, these techniques also tend to enhance cognitive executive functioning. Recent developments and future research possibilities concerning the application of rTMS in the treatment of alcohol addiction will be discussed.

Stijging in de prevalentie van autismespectrumstoornissen: feit of fictie?

Autisme is een ontwikkelingsstoornis die zich kenmerkt door tekortkomingen op het vlak van communicatie en sociale interactie, alsook door de aanwezigheid van beperkte en zich herhalende, stereotiepe patronen van gedrag en/of interesses. Een recente toename in het diagnosticeren van autismespectrumstoornissen (ASS) bij volwassenen brengt deze problematiek onder de aandacht. Mogelijke verklaringen en hypothesen voor de vastgestelde stijging in prevalentie worden toegelicht aan de hand van een literatuurstudie.