Figure 1
PRISMA flowchart of the systematic review update.
Table 1A
Movement disorders in CNS-WhD patients suffering from at least one MD or SGP.
| TOTAL (n = 168) | SINGLE CASE (n = 130) | SINGLE CASE % (IF TOTALNOT 130) | CASE SERIES (n = 38) | CASE SERIES % | |
|---|---|---|---|---|---|
| Age at MD onset (if specified; otherwise at first CNS sign onset or first hospital consultation), years | 49.4 | 49.8 | – | 48.3 | – |
| Men | 129 | 102 | 78 | 27 | 71 |
| Women | 39 | 28 | 22 | 11 | 29 |
| Myoclonus (including myorhythmia): total | 77 | 69a | 53 | 8 | 21 |
| I. Myorhythmia: totala | 57 | 52b | 40 | 5 | 13 |
| 1. OMM and OFSM: rhythmic pendular convergent-divergent or vertical nystagmus associated with masticatory or facioskeletal myorhythmia | 36 | 32 | 25 | 4 | 11 |
| a. Vergence component mentioned | 9 | 19 | 83 (23) | NA | NA |
| b. Vertical component mentioned | 4 | 4 | 17 (23) | NA | NA |
| c. Involving palate at the same frequency | 2 | 2 | 6 (32) | NA | NA |
| d. Persistence in sleep mentioned | 9 | 9 | 28 (32) | NA | NA |
| 2. Isolated ocular myorhythmia not associated with masticatory or facioskeletal myorhythmia | 4 | 4 | 3 | 0 | 0 |
| 3. Myorhythmia (either rhythmic, continuous, or the word myorhythmia was used by the authors) of branchial/spinal muscles without any ocular involvement | 17 | 17 | 13 | 0 | 0 |
| a. Branchial muscles | 6 | 6 | 35 (17) | NA | NA |
| b. Spinal muscles | 8 | 8 | 47 (17) | NA | NA |
| c. Both branchial and spinal muscles | 3 | 3 | 18 (17) | NA | NA |
| II. Arrhythmic myoclonus: only nonrhythmic forms or not specified whether rhythmic or notb | 21 | 18 | 14 | 3 | 8 |
| a. Branchial muscles | 2 | 2 | 12 (17) | NA | NA |
| b. Spinal muscles | 5 | 5 | 29 (17) | NA | NA |
| c. Both branchial and spinal muscles or not specified | 11 | 11 | 65 (17) | NA | NA |
| Stimulus-sensitivity specified | 1 | 1 | 6 (17) | NA | NA |
| Ataxia: total | 72 | 52 | 40 | 20 | 53 |
| 1. Appendicular ataxia: total/isolated | 28 | 24|12 | 18|9 | 4/NA | 11/NA |
| 2. Axial ataxia: total/isolated | 29 | 24|12 | 18|9 | 5/NA | 13/NA |
| 3. Both appendicular and axial ataxia | 12 | 12 | 9 | NA | NA |
| 4. Unspecified ataxia | 27 | 16 | 12 | 11 | 29 |
| Gait and balance abnormalities: total | 67 | 60 | 46 | 7 | 18 |
| 1. Gait problems (any type) | 46 | 41 | 32 | 5 | 13 |
| 2. Postural/balance issues (any type) and/or falls | 31 | 29 | 22 | 2 | 5 |
| 3. Both | 10 | 10 | 8 | NA | NA |
| Other movement disorders ranked in frequency | |||||
| 1a. Parkinsonism (all possible cases) | 25 | 17 | 13 | 8 | 21 |
| 1b. Parkinsonism (only unequivocal) | 7 | 6 | 5 | 1 | 3 |
| 2. Tremor | 13 | 10 | 8 | 3 | 8 |
| 3. Dystonia (including 4 with isolated blepharospasm) | 8 | 7 | 5 | 1 | 3 |
| 4. Bruxism | 3 | 3 | 2 | 0 | 0 |
| 5. Chorea | 3 | 1 | 1 | 2 | 5 |
[i] Except for the age row and the percentage columns, all numbers refer to number of cases.
Percentages are highlighted in bold when the number of patients is large enough for percentages to be considered relevant.
a. 32 + 4 + 17 = 53, but total of patients is 52 because one patient had first isolated ocular then isolated facial myorhythmia.
b. There were 18 arrhythmic myoclonus + 52 myorhythmia = 70, but total number of patients was 69 because 1 patient had both arrhythmic myoclonus and myorhythmia.
NA, not applicable because of pooling of information in the case series.
Table 1B
Ocular motility disorders in CNS-WhD patients suffering from at least one MD or SGP.
| TOTAL (n = 168) | SINGLE CASE (n = 130) | SINGLE CASE % (IF TOTALNOT 130) | CASE SERIES (n = 38) | CASE SERIES % | |
|---|---|---|---|---|---|
| Ocular motility palsies/paresis | |||||
| 1. Total SGP | 87 | 75 | 58 | 12 | 32 |
| a. Associated with at least one MD | 62 | 62 | 83 (75) | NA | NA |
| b. Not associated with any MD | 13 | 13 | 17 (75) | NA | NA |
| 2. Vertical SGP | 65 | 62 | 48 | 3 | 8 |
| a. Vertical alone | 28 | 26 | 42 (62) | 2 | 67 (3) |
| b. Associated with horizontal | 37 | 36 | 58 (62) | 1 | 33 (3) |
| 3. SGP not specified whether vertical or horizontal | 22 | 13 | 10 | 9 | 24 |
| 4. Isolated horizontal gaze palsy (not specified whether supranuclear) | 2 | 2 | 2 | 0 | 0 |
| 5. Non–supranuclear palsies/paresis (isolated palsy of any of the 3 oculomotor nerves or mention of diplopia; blurred vision excluded, as it lacks precision regarding its cause) | 29 | 29 | 22 | 0 | 0 |
| Spontaneous involuntary eye movements: total | 53 | 48 | 37 | 5 | 13 |
| 1. OMM and OFSM | See table 1A | See table 1A | – | See table 1A | – |
| 2. Isolated ocular myorhythmia | See table 1A | See table 1A | – | See table 1A | – |
| 3. Other involuntary eye movements (mostly nystagmus) | 13 | 12 | 9 | 1 | 3 |
[i] Except for the percentages’ columns, all numbers refer to number of cases.
Percentages are highlighted in bold when the number of patients is large enough for percentages to be considered relevant.
NA, not applicable because of pooling of information in the case series.
Table 2
Laboratory, imaging, and electroencephalographic findings in CNS-WhD patients suffering from at least one MD or SGP.
| SINGLE CASE (n = 130) | POSITIVITY % | CASE SERIES (n = 38) | POSITIVITY% | |
|---|---|---|---|---|
| Laboratory/microscopy | ||||
| CSF pleocytosis (>5 cells/mm3): present/total number reported | 44|93 | 47 | 6|16 | 38 |
| CSF protein elevation (>0,45 g/L): present/total number reported | 36|89 | 40 | 7|16 | 44 |
| CSF PAS: positive/total number reported | 10|27 | 37 | 2|2 | 100 |
| CSF PCR: positive/total number reported | 34|48 | 71 | 11|12 | 92 |
| Blood PCR: positive/total number reported | 11|18 | 61 | 0|0 | NA |
| Gut PAS: positive/total number reported | 44|84 | 52 | 19a|28 | 68 |
| Gut PCR: positive/total number reported | 14|24 | 58 | 14|16 | 88 |
| Lymph-node PAS: positive/total number reported | 11|14 | 79 | 0|0 | NA |
| Lymph node PCR: positive/total number reported | 2|3 | 67 | 0|0 | NA |
| Brain (biopsy or autopsy) PAS: positive/total number reported | 37|39 | 95 | 9|9 | 100 |
| Brain (biopsy or autopsy) PCR: positive/total number reported | 4|6 | 67 | 0|0 | NA |
| Electron microscopy (EM): positive/total number reported | 24|29 | 83 | 1|1 | 100 |
| 1. Gut EM: positive (% over 24 — respectively 1 — cases) | 12 | 50 | 1 | 100 |
| 2. Brain EM: positive (% over 24 cases) | 11 | 46 | 0 | 0 |
| 3. CSF EM: positive (% over 24 cases) | 1 | 4 | 0 | 0 |
| 4. Lymph nodes EM: positive (% over 24 cases) | 2 | 8 | 0 | 0 |
| Brain imaging | ||||
| Brain-CT: abnormal/total number reported | 20|40 | 50 | NA | NA |
| Type of abnormality | ||||
| 1. Atrophy (% over 20 cases) | 7 | 35 | – | – |
| 2. Lesion (hypodensity or mass-like) (% over 20 cases) | 10 | 50 | – | – |
| 3. Enhancement (% over 20 cases) | 5 | 25 | – | – |
| Brain MRI: abnormal/total number reported | 71|82 | 87 | NA | NA |
| Type of abnormality | ||||
| 1. Atrophy (%over 71 cases) | 11 | 15 | – | – |
| 2. Lesion (either spontaneous T2 hyperintensity or mass-like lesion) (% over 71 cases) | 55 | 77 | – | – |
| 3. Enhancement (%over 71 cases) | 17 | 24 | – | – |
| 4. other/nonspecific (%over 71 cases) | 8 | 11 | – | – |
| Electroencephalography (EEG) | ||||
| EEG: abnormal/total number reported | 31|54 | 57 | NA | NA |
| 1. Epileptiform discharges (% over 31 cases) | 7 | 23 | – | – |
| 2. Non pecific abnormalities (% over 31 cases) | 24 | 77 | – | – |
[i] Except for the percentages’ columns, all numbers refer to number of patients.
Percentages are highlighted in bold when the number of patients is large enough for percentages to be considered relevant.
a: Imprecise number because of methodological issues of 1 case series: means “up to 19 positive PAS staining in the gut.”
NA, not applicable.
Table 3
Treatment outcome and antibiotics used in 130 CNS-WhD suffering from at least one MD or SGP.
| OUTCOME / ANTIBIOTICS | SINGLE CASES | % |
|---|---|---|
| Outcome | n = 130 | |
| 1. Improvement (from partial to good) | 64 | 49 |
| 2. No improvement/worsening | 13 | 10 |
| 3. Death | 32 | 25 |
| 4. Not specifically mentioned if the clinical picture improved | 21 | 16 |
| Pooling categories into good and bad outcomes | n = 109a | |
| 1. good outcome | 64 | 59 |
| 2. bad outcome (no improvement/worsening/death) | 45 | 41 |
| Antibiotics | n = 103b, c | |
| 1. Trimethoprim-sulfamethoxazole | 72 | 70 |
| 2. Ceftriaxone | 53 | 51 |
| 3. Penicillin (any type) | 20 | 19 |
| 4. Chloramphenicol | 16 | 16 |
| 5. Tetracycline | 23 | 22 |
| 6. Streptomycin | 13 | 13 |
| 7. Doxycycline (twice with hydroxychloroquine) | 20 | 19 |
[i] a. n = 109 because we excluded cases for whom outcome was not reported.
b. No antibiotics used or not mentioned what antibiotics were used in n = 27; total cases = 103.
c. Most frequent antibiotics are used in combination.