Downregulation of LKB1/AMPK Signaling in Blood Mononuclear Cells Is Associated with the Severity of Guillain-Barre Syndrome.

AMP-activated protein kinase (AMPK) is an intracellular energy sensor that regulates metabolic and immune functions mainly through the inhibition of the mechanistic target of rapamycin (mTOR)-dependent anabolic pathways and the activation of catabolic processes such as autophagy. The AMPK/mTOR signaling pathway and autophagy markers were analyzed by immunoblotting in blood mononuclear cells of 20 healthy control subjects and 23 patients with an acute demyelinating form of Guillain-Barré syndrome (GBS). The activation of the liver kinase B1 (LKB1)/AMPK/Raptor signaling axis was significantly reduced in GBS compared to control subjects. In contrast, the phosphorylated forms of mTOR activator AKT and mTOR substrate 4EBP1, as well as the levels of autophagy markers LC3-II, beclin-1, ATG5, p62/sequestosome 1, and NBR1 were similar between the two groups. The downregulation of LKB1/AMPK signaling, but not the activation status of the AKT/mTOR/4EBP1 pathway or the levels of autophagy markers, correlated with higher clinical activity and worse outcomes of GBS. A retrospective study in a diabetic cohort of GBS patients demonstrated that treatment with AMPK activator metformin was associated with milder GBS compared to insulin/sulphonylurea therapy. In conclusion, the impairment of the LKB1/AMPK pathway might contribute to the development/progression of GBS, thus representing a potential therapeutic target in this immune-mediated peripheral polyneuropathy.

Responsiveness of 2 Different Ability Outcome Measures in Guillain-Barré Syndrome.

BACKGROUND: The most frequently used ability outcome measure in Guillain-Barré syndrome (GBS) is the GBS disability scale (GDS). Recently developed inflammatory Rasch-built overall disability (I-RODS) scale has been suggested to be used in inflammatory polyneuropathies. In the present study, we wanted to assess the comparative responsiveness of I-RODS and GDS in subjects who were diagnosed with GBS during a follow-up period of 6 months. METHODS: Our prospective, multicentric study included 72 subjects. Patients were tested, using GDS and I-RODS, on day 14, day 28, month 3, and month 6 from the start of the symptoms. We defined improvement as a reduction for 1 or more points on GDS or improvement on I-RODS as defined by Draak (2014). RESULTS: Between days 14 and 28 there was an improvement in 28% of patients as measured with GDS and only in 10% patients as measured with I-RODS. At month 3 compared with day 14, we noticed an improvement in GDS score in 90% of GBS patients and I-RODS score in 65%. At month 6 improvements were noticed in 94% of patients measured by GDS and 78% according to I-RODS. CONCLUSION: Our findings support the use of GDS in an acute phase of GBS. I-RODS have their role mostly during a longer follow-up period when the majority of patients are ambulant and their other abilities besides walking are also of great importance.

Non-convulsive status epilepticus as an initial manifestation of herpes simplex virus encephalitis.

Herpes simplex encephalitis (HSVE), manifesting with non-convulsive status epilepticus (NCSE), normocellular CSF findings and CT features of acute ischemic stroke, is a rare finding that can be hard to diagnose accurately. We present a case of HSVE and compare our results to those of previously published cases with the same pathology, in order to provide information to support more rapid and effective diagnosis and treatment. A Pubmed search of reported cases was conducted and five cases of HSVE manifesting with NCSE were found. Each of the cases, including ours, was compared in terms of clinical manifestations and CSF, CT and EEG findings. The clinical manifestations in our patient correlated with those of the other cases. EEG showing sharp fronto-temporo-centro-parietal waves was only observed in our patient. Similar CT manifestations were found in one other patient, normocellular CSF was registered in three other cases and positive PCR for HSV in four patients. Information about the possible clinical manifestations and CT, EEG and CSF findings in patients with HSVE manifesting with NCSE is crucial for a fast diagnosis and successful treatment, leading to higher survival rates and fewer complications and neurological deficits.

Rate of progression of Guillain-Barré syndrome is not associated with the short-term outcome of the disease.

INTRODUCTION: There are no many data on association between progression rate of Guillain-Barré syndrome (GBS) and disease outcome. AIM: The aim of our study was to analyze short-term outcome of GBS in relation to the rate of disease progression. METHODS: Our retrospective study included patients diagnosed with GBS in seven tertiary healthcare centers from 2009 to 2014. According to the rate of disease progression from onset of symptoms to the nadir, patients were divided in three groups: rapid-onset GBS (nadir reached in maximum 48 h), gradual-onset (nadir reached in three to 14 days), and slow-onset (nadir in 15 to 28 days). GBS disability scale (GDS) was used to assess functional disability at nadir and on discharge. RESULTS: Among 380 patients included in the study, 24 (6.3%) patients had rapid-onset, 274 (72.1%) gradual-onset, and 82 (21.6%) slow-onset GBS. Time from the onset of the disease to the hospital admission was much shorter in faster-onset forms (3.0 ± 4.1 days in rapid-onset vs. 6.8 ± 9.5 days in gradual-onset and 21.0 ± 9.6 days in slow-onset GBS, p < 0.01). Preceding events were less commonly identified in slow-onset forms. Patients with rapid-onset GBS were more likely to have axonal variants (p < 0.05). All three groups of patients were treated in a similar way, and there were no differences in GDS score at nadir (p > 0.05) and on discharge (p > 0.05) and no differences in the duration of hospital stay. CONCLUSION: Faster progression of GBS does not imply a poorer short-term functional outcome of the disease.

Self-reported autonomic dysfunction in a recovery phase of Guillain-Barré syndrome.

OBJECTIVE: Autonomic dysfunction occurs in approximately two-thirds of Guillain-Barré syndrome (GBS) patients in the acute phase of the disease. Although improving over time, subclinical autonomic involvement may be present for 3-8 years after the GBS episode. The aim of this study was to determine the frequency of self-reported autonomic disorders in GBS patients three and six months after disease onset compared to healthy controls (HCs). METHODS: Our study included adult patients diagnosed with GBS from May 2017 until May 2018 in seven healthcare centers (67.6 % with demyelinating and 13.6 % with axonal syubtype). Functional disability was assessed by the Guillain-Barré syndrome disability scale (GDS). Each subject filled in the Serbian version of the SCOPA-Aut questionnaire. Using GDS and SCOPA-Aut, patients were tested at month 3 (M3) (n = 71) and month 6 (M6) (n = 70) from symptom onset. RESULTS: Dysautonomia was more common in patients with GBS compared to HCs at M3 (p < 0.01), while there was no difference at M6 (p > 0.05). Among autonomic disorders, constipation, complications to pass stool, and orthostatic hypotension were the most frequently reported. Patients with axonal variants had worse total SCOPA-Aut scores at M3 in comparison to AIDP patients (11.7 ± 10.1 vs. 6.1 ± 5.1, p < 0.05). GDS score correlated with the total SCOPA-Aut score. CONCLUSION: Autonomic symptoms are common in GBS patients during the recovery phase. They are more pronounced in patients with axonal forms of GBS and those with a higher degree of functional disability.

Incidence and mortality rates of Guillain-Barré syndrome in Serbia.

Guillain-Barré syndrome (GBS) is an acute auto-immune polyradiculoneuropathy. A huge variety of GBS incidence and mortality rates has been noted across the world. The objective of the present multi-centric study was to assess the incidence and mortality rates of GBS during a 10-year period in Serbia. We collected data of adult GBS patients who were hospitalized from 2009 to 2018 in all five tertiary healthcare centers in Serbia. The incidence rates per 100 000 inhabitants with 95% confidence intervals (CI) were calculated and further corrected for the estimated number of patients hospitalized in secondary centers. Mortality rates were also assessed. GBS was considered severe if patients were not able to walk at least 10 m without assistance. Six hundred and forty GBS patients were registered in tertiary centers in a 10-year period. The proportion of severe cases was 75% at nadir, and 52% on discharge. GBS incidence rate in Serbia was 1.1 per 100 000 inhabitants, and estimated incidence if patients from secondary centers included 1.2 per 100 000. Peak incidence was observed during the sixth decade of life. During the acute phase, 5.6% of GBS patients died, while overall 9.7% of them died during 6-month period from disease onset. This study contributes to our knowledge about GBS epidemiology. Results will allow us to improve the diagnosis and treatment of GBS patients in Serbia.

Disability and quality of life in Guillain-Barré syndrome - Longitudinal study.

Longitudinal health-related quality of life (QoL) data in Guillain-Barré (GBS) patients are still scarce. We, therefore, investigated health- related QoL in GBS patients from Serbia and surrounding countries during a six-month follow-up period, and analyzed its association with patients' disability. Our study comprised 74 adult patients diagnosed with GBS from May 2017 until May 2018 in seven tertiary healthcare centers. Health-related QoL was investigated using the SF-36 questionnaire, and compared with functional disability assessed by the GBS disability scale (GDS). Tests were performed at day 14, day 28, month 3 and month 6 from disease onset. GDS and SF-36 scores improved over time (p < 0.01). GDS scores were different at all four time points, while SF-36 did not differ between day 14 and day 28. Pooled SF-36 scores (especially physical ones) correlated with pooled GDS scores, except for Bodily Pain and Role Emotional scores. We found that GDS score at day 14 was an independent predictor of GDS score at month 6 (ß = +0.52, p < 0.01), while SF-36 score at day 14 was an independent predictor of SF-36 score at month 6 (ß = +0.51, p < 0.01). Neurologists should look not only on disability but also on QoL in GBS patients, since these two measures provide us with important complementary items of information.

Six-month prospective study of quality of life in Guillain-Barre syndrome.

OBJECTIVE: Guillain-Barre syndrome (GBS) is an acute disease of the peripheral nerves and their roots. Quality of life (QoL) in the first year after acute episode of GBS is still underresearched area. The aim of our study was to investigate QoL in GBS patients during a 6-month follow-up period. METHODS: Multicentric, prospective study included 74 adult patients with GBS (54% males). GBS disability scale (GDS) was used to assess functional disability (severe disability GDS > 2), and Individualized Neuromuscular Quality of Life Questionnaire (INQoL) to asses QoL. Patients were tested on day 14, day 28, month 3, and month 6 from symptom onset. RESULTS: Disability as measured by GDS improved during time (P < .01). INQoL scores also improved during time (P < .01) but were not able to differentiate between day 14 and day 28, and some scores also did not make difference between month 3 and 6 (pain, social relations, emotions and total INQoL score; P > .05). Pooled GDS scores correlated with pooled INQoL scores, especially with independence, activities, and weakness subscores (P < .01). Multiple linear regression analysis showed that GDS at day 14 (ß = .52, P < .01) and fatigue score at day 14 (ß = .41, P < .01) were independent predictors of the worse GDS at month 6 (adjusted R2  = .34, P < .01 for overall model). CONCLUSIONS: During a 6-month follow-up period of GBS patients, we observed a gradual recovery of patients' disability and QoL. Our study confirms the importance of patient-reported outcomes and their ability to capture some important issues that are omitted by classic ability measures such as GDS.