It is a Luminal B. According to the SEGO, this patient is a candidate for chemotherapy treatment because of the high histologic grade and high tumor proliferation.

A 64-year-old woman, without relevant comorbidities, operated on for a right breast cancer by means of an extended lumpectomy and selective sentinel lymph node biopsy, with the following anatomopathological result: Infiltrating ductal carcinoma poorly dlferentiated (grade 3), size 2.2 cm (pT2), estrogen and progesterone receptor positive, Ki67 25%, HER2 negative. There is macroscopic involvement of the sentinel lymph node, although there is no involvement of the rest of the isolated axillary nodes (pN1). What adjuvant systemic treatment do you consider most appropriate for this patient?

Adjuvant hormone therapy including aromatase inhibitors.

Adjuvant chemotherapy, preferably with anthracyclines and taxanes, followed by hormone therapy.

Adjuvant chemotherapy in association with the monoclonal antibody trastuzumab, followed by hormone therapy.

Adjuvant chemotherapy, preferably with anthracyclines and taxanes.

Maximizing the Clinical Benefit of Anthracyclines in Addition to Taxanes in the Adjuvant Treatment of Early Breast Cancer.

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A healthy 56-year-old postmenopausal woman discovered a palpable mass at the one o'clock position of the left breast. After an initial biopsy confirmed breast cancer, she underwent mastectomy and axillary node dissection for a left-sided breast cancer that measured 3.5 cm. There was extensive lymphovascular invasion. Pathology review indicated a poorly differentiated, grade 3 invasive ductal carcinoma and ductal carcinoma in situ (largest focus, 3.5 cm). The margins were negative. Two of the 11 axillary lymph nodes contained metastatic carcinoma. Immunohistochemical studies previously obtained on the core biopsy indicated that the tumor was positive for estrogen receptor expression (50%), negative for progesterone receptor expression, and had a Ki-67 score of 60%. There was no amplification of the human epidermal growth factor receptor 2/ neu gene. Staging scans were negative for metastatic disease. Our multidisciplinary tumor board recommended adjuvant chemotherapy, postmastectomy radiation therapy, and endocrine therapy. A 52-year-old postmenopausal woman presented with a palpable mass of the right breast. An initial core biopsy confirmed carcinoma in the breast. She underwent quadrantectomy and axillary node dissection. The final pathology report disclosed a moderately differentiated invasive ductal carcinoma (diameter, 2.5 cm). The margins were negative. None of the three sentinel lymph nodes contained metastatic carcinoma. Immunohistochemical studies showed that the tumor was positive for estrogen receptor expression (90%) and for progesterone receptor expression (40%) and had a Ki-67 score of 20%. There was no amplification of the human epidermal growth factor receptor 2/ neu gene. Staging scans were negative for metastatic disease. A genomic assay was obtained and suggested an intermediate to high risk of recurrence. Her past medical history was notable for hypertension and moderately overweight status (body mass index, 39 kg/m<sup2</sup). Our multidisciplinary tumor board recommended adjuvant chemotherapy, postsurgical radiation therapy, and endocrine therapy.

Invasive carcinoma of no special type

Overall, the five-year survival rate of invasive ductal carcinoma was approximately 85% in 2003. Treatment Treatment of invasive carcinoma of no special type (NST) depends on the size of the mass (size of the tumor measured in its longest direction): <4 cm mass: surgery to remove the main tumor mass and to sample the lymph nodes in the axilla. The stage of the tumor is ascertained after this first surgery. Adjuvant therapy (i.e., treatment after surgery) may include a combination of chemotherapy, radiotherapy, hormonal therapy (e.g., tamoxifen) and/or targeted therapy (e.g., trastuzumab). More surgery is occasionally needed to complete the removal of the initial tumor or to remove recurrences. 4 cm or larger mass: modified (a less aggressive form of radical mastectomy) radical mastectomy (because any malignant mass in excess of 4 cm in size exceeds the criteria for a lumpectomy) along with sampling of the lymph nodes in the axilla.

Biological characterization and selection criteria of adjuvant chemotherapy for early breast cancer: experience from the Italian observational NEMESI study.

International treatment guidelines recommend administration of adjuvant chemotherapy in early breast cancer based on clinical, prognostic and predictive parameters. An observational study (NEMESI) was conducted in 63 Italian oncology centres in patients with early breast cancer. Age, performance status, concomitant disease, menopausal status, histology, tumor dimension (pT), axillary lymph node status (pN), grading (G), estrogen and progesterone receptor (ER and PgR), proliferative index (ki67 or MIB-1), human epidermal growth factor receptor 2 (HER2) and type of adjuvant treatment were recorded. The primary objective of the study was to define parameters influencing the decision to prescribe adjuvant chemotherapy and the type of chemotherapy. Data for 1894 patients were available. 69.0% postmenopausal, 67.0% pT1, 22.3% pTmic/pT1a/pT1b, 61.0% pN0, 48.7% luminal A, 18.1% luminal B, 16.1% HER2 positive, 8.7% triple negative, 8.4% unknown. 57.8% received adjuvant chemotherapy: 38.1% of luminal A, 67.3% luminal B, 88.2% HER2-positive, 97.6% triple negative. Regimens administered: 9.1% CMF-like, 48.8% anthracyclines, 38.4% anthracyclines plus taxanes, 3.7% taxanes alone. Increasing pT/pN and, marginally, HER2-positive were associated with the prescription of anthracyclines plus taxanes. Suboptimal schedules (CMF-like or AC/EC or FEC-75) were prescribed in 37.3% receiving chemotherapy, even in HER2-positive and triple negative disease (36.5% and 34.0%, respectively). This study showed an overprescription of adjuvant chemotherapy for early breast cancer, particularly referred to luminal A. pT, pN and, marginally, HER2 were the principal determinants for the choice of chemotherapy type. Suboptimal chemotherapy regimens were adopted in at least one third of HER2-positive and triple negative.

Nodal staging affects adjuvant treatment choices in elderly patients with clinically node-negative, estrogen receptor-positive breast cancer.

In response to Choosing Wisely recommendations that sentinel lymph node biopsy (slnb) should not be routinely performed in elderly patients with node-negative (cN0), estrogen receptor-positive (er+) breast cancer, we sought to evaluate how nodal staging affects adjuvant treatment in this population. From a prospective database, we identified patients 70 or more years of age with cN0 breast cancer treated with surgery for er+ her2-negative invasive disease during 2012-2016. We determined rates of, and factors associated with, nodal positivity (pN+), and compared the use of adjuvant radiation (rt) and systemic therapy by nodal status. Of 364 patients who met the inclusion criteria, 331 (91%) underwent slnb, with 75 (23%) being pN+. Axillary node dissection was performed in 11 patients (3%). On multivariate analysis, tumour size was the only factor associated with pN+ (<ip</i = 0.007). Nodal positivity rates were 0%, 13%, 23%, 33%, and 27% for lesions preoperatively sized at 0-0.5 cm, 0.5-1 cm, 1.1-2.0 cm, 2.1-5.0 cm, and more than 5.0 cm. Compared with patients assessed as node-negative, those who were pN+ were more likely to receive axillary rt (lumpectomy: 53% vs. 1%, <ip</i < 0.001; mastectomy: 43% vs. 2%, <ip</i < 0.001), and adjuvant systemic therapy (endocrine: 82% vs. 69%; chemotherapy plus endocrine: 7% vs. 2%, <ip</i = 0.002). Of elderly patients with cN0 er+ breast cancer, 23% were pN+ on slnb. Size was the primary predictor of nodal status, and yet significant rates of nodal positivity were observed even in tumours preoperatively sized at 1 cm or less. The use of rt and systemic adjuvant therapies differed by nodal status, although the long-term oncologic implications require further investigation. Multidisciplinary input on a case-by-case basis should be considered before omission of slnb.

Male breast cancer

Treatment Treatment largely follows patterns that have been set for the management of postmenopausal breast cancer. The initial treatment is surgical and consists of a modified radical mastectomy with axillary dissection or lumpectomy and radiation therapy with similar treatment results as in females. Also, mastectomy with sentinel lymph node biopsy is a treatment option. In males with node-negative tumors, adjuvant therapy is applied under the same considerations as in females with node-negative breast cancer. Similarly, with node-positive tumors, males increase survival using the same adjuvants as affected females, namely both chemotherapy plus tamoxifen and other hormonal therapy. There are no controlled studies in males comparing adjuvant options. In the vast majority of males with breast cancer hormone receptor studies are positive, and those situations are typically treated with hormonal therapy.

Clinical outcome of breast cancer patients with N3a (≥10 positive lymph nodes) disease: has it changed over years?

It has been shown that breast cancer patients with N3a (10 positive lymph nodes) had a poor prognosis. We planned to investigate the clinical outcome BC patients who presented with N3a disease and had no evidence of systemic metastasis at the time of diagnosis. We made a retrospective chart review of breast cancer patients who had ≥10 positive lymph nodes and received adjuvant systemic therapy in Marmara University Hospital between 1998 and 2008. We recorded clinical, pathologic and treatment characteristics of the patients and analyzed the survival outcome. We identified 73 patients with N3a disease who were treated in Marmara University Hospital between 1998 and 2008. The median age was 52. Most (75%) of the patients had invasive ductal histology, 75% had T2/T3 tumors, 36% had grade 3 tumors. The median number of metastatic lymph nodes was 15. Estrogen and progesterone receptors were both positive in 61% and both negative in 16+ tumors. Her-2/neu status was assessed in 68% of the tumors; 18% of patients had 3+ and 50% had negative scores. Six patients had triple negative tumors. All patients except one received adjuvant chemotherapy and radiotherapy. Seventy-four percent of patients received anthracycline/taxane-based chemotherapy. Fifty-nine patients received adjuvant endocrine therapy, 42% them received aromatase inhibitors. Five of the 13 Her-2 positive patients received adjuvant trastuzumab. With a median follow-up of 47 months, 5-year disease and overall survival rates were 66 and 81%, respectively. Twenty-four patients had relapsed and 14 patients died. Her-2 status and the number of lymph nodes (<20 vs. ≥20) had significant impact on disease-free survival in the univariate analysis (P=0.03 and 0.05, respectively) and Her-2 retained its significant impact on disease-free survival in the multivariate analysis (P=0.05). The prognosis of BC patients with N3a disease has changed favorably in the past decade with the current standards of care.

Lumpectomy

After a lumpectomy is performed for DCIS, local radiation therapy is typically performed to help eliminate microscopic-level disease. Axillary sentinel lymph node biopsy, as a method of screening for metastatic disease in otherwise non-invasive DCIS, is falling out of favor because the risks of procedure outweigh any effect on outcomes. For DCIS, chemotherapy is not recommended, but tamoxifen may be recommended for tumors which contain an abundance of estrogen receptors. For patients with invasive ductal carcinoma who have lumpectomies, lymph node biopsy and radiation therapy are usually recommended. Adjuvant chemotherapy is often recommended, but it may not be recommended if the tumor is small and there are no lymph node metastases. For larger tumors, neoadjuvant chemotherapy may be recommended.

Does the result of completion axillary lymph node dissection influence the recommendation for adjuvant treatment in sentinel lymph node-positive patients?

The Hungarian National Institute of Oncology has just closed a single-center randomized clinical study. The Optimal Treatment of the Axilla-Surgery or Radiotherapy (OTOASOR) trial compares completion axillary lymph node dissection (cALND) with regional nodal irradiation (RNI) in patients with sentinel lymph node-positive (SLN+) primary invasive breast cancer. In the investigational treatment arm, patients received 50 Gy RNI instead of cALND. In these patients we had information only about the sentinel lymph node (SLN) status, but the further axillary nodal involvement remained unknown. The aim of this study was to investigate whether the result of cALND influenced the recommendation for adjuvant treatment in patients with SLN+ breast cancer. Patients with SLN+ primary breast cancer were randomized for cALND (arm A, standard treatment) or RNI (arm B, investigational treatment). Adjuvant systemic treatments were given according to the standard institutional protocol, and patients were followed according to the actual institutional guidelines. Between August 2002 and June 2009, 474 SLN+ patients were randomized to cALND (arm A, standard treatment = 244 patients) or RNI (arm B, investigational treatment = 230 patients). The 2 arms were well balanced according to the majority of main prognostic factors. However, more patients were premenopausal (34% vs. 27%; P = .095) and had pT2-3 tumors (57% vs. 40%; P = .003) in the completion axillary lymph node dissection (ALND) arm. On the other hand, there were more patients with known human epidermal growth factor receptor type 2 positive tumor (12% vs. 17%, P = .066) in the RNI arm. In the ALND and RNI arms, 78% (190/244) and 69% (159/230), respectively, received chemotherapy (P = .020). Endocrine therapy was administered in 87% (213/244) of the patients in the ALND arm and 89% (204/230) of the patients in the RNI arm (P = .372). Six patients (2.5%) on arm A and 13 patients (5.7%) on arm B received adjuvant trastuzumab treatment (P = not significant). Subgroup analyses explored that more frequent administration of adjuvant chemotherapy in arm A was associated with the higher percentage of premenopausal patients and patients with larger (pT2-3) tumors. The result of cALND after positive SLN biopsy seems to have no major impact on the administration of adjuvant systemic therapy.

Adjuvant therapy

Breast cancer It has been known for at least 30 years that adjuvant chemotherapy increases the relapse-free survival rate for patients with breast cancer In 2001 after a national consensus conference, a US National Institute of Health panel concluded: “Because adjuvant polychemotherapy improves survival, it should be recommended to the majority of women with localized breast cancer regardless of lymph node, menopausal, or hormone receptor status.” Agents used include: However, ethical concerns have been raised about the magnitude of benefit of this therapy since it involves further treatment of patients without knowing the possibility of relapse. Dr. Bernard Fisher, among the first to conduct a clinical trial evaluating the efficacy of adjuvant therapy on patients with breast cancer, described it as a "value judgement" in which the potential benefits must be evaluated against the toxicity and cost of treatment and other potential side effects.

Breast International Group

BIG clinical trials and research programmes Over the years, BIG has developed and successfully run numerous large, phase 3 clinical trials involving thousands of international investigators and institutions. These clinical trials include HERA (HERceptin Adjuvant), MINDACT (Microarray In Node-Negative and 1 to 3 Positive Lymph Node Disease May Avoid Chemotherapy), and ALTTO (Adjuvant Lapatinib and/or Trastuzumab Treatment Optimisation). Many BIG studies have been practice-changing, for example, putting aromatase inhibitors on the map (BIG 1-98), changing how we treat young women with breast cancer (SOFT), leading to a major breakthrough in treating HER2-positive breast cancer (HERA), or helping physicians evaluate which women with early breast cancer could be spared chemotherapy after surgery (MINDACT). Most BIG trials incorporate a substantial translational research component and emphasise the collection and banking of biological specimens for the purpose of future research.

[Two cases of recurrent breast cancer with regional lymph node metastases showing a complete response to trastuzumab and paclitaxel treatment].

We report two cases of recurrent breast cancer with regional lymph node metastases that responded completely to treatment with trastuzumab and paclitaxel. Case 1: A 52-year-old woman, who presented with left breast cancer, underwent mastectomy and axillary lymph node dissection in July 2002. Pathological findings were as follows: invasive ductal carcinoma (scirrhous type), 2.2 cm in size, histological grade 3, positive invasion to the lymphatic and blood vessels, negative nodal status (0/11), negative ER/PgR status, and overexpression of HER 2/neu. Left axillary lymph node metastasis was noted after five months, ie, in December 2002. Four cycles of chemotherapy with doxorubicin and cyclophosphamide were administered from January 2003; however, they were not effective. The patient showed a complete response after three months of chemotherapy with trastuzumab and paclitaxel. This treatment was stopped in September 2003. She has maintained a complete response for two and a half years and was not administered any further treatment as of February 2006. Case 2: A 59-year-old woman, who presented with right breast cancer, underwent mastectomy and axillary lymph node dissection in May 2002. Pathological findings were as follows: invasive ductal carcinoma (scirrhous type), 1.8 cm in size, histological grade 2, positive invasion to the lymphatic and blood vessels, negative nodal status (0/5), positive ER and uncertain PgR status, and overexpression of HER 2/neu. She had received adjuvant hormonal therapy with tamoxifen; however, a right supraclavicular lymph node metastasis was noted in October 2004. Treatment with exemestane was not effective. However, a complete response was observed with trastuzumab and paclitaxel for four months. She has maintained a complete response for six months and was not administered any further treatment as of February 2006.

Paget's disease of the breast

In most cases, adjuvant treatment is part of the treatment schema. This type of treatment is normally given to patients with cancer to prevent a potential recurrence of the disease. Whether adjuvant therapy is needed depends upon the type of cancer and whether the cancer cells have spread to the lymph nodes. In Paget's disease, the most common type of adjuvant therapy is radiation following breast-conservative surgery. Adjuvant therapy may also consist of anticancer drugs or hormone therapies. Hormonal therapy reduces the production of hormones within the body, or prevents the hormones from stimulating the cancer cells to grow, and it is commonly used in cases of invasive cancer by means of drugs such as tamoxifen and anastrozole.

[San Antonio Breast Cancer Symposium -- highlights 2004].

The adjuvant therapy of postmenopausal, hormonereceptor positive breast cancer patients with aromatase inhibitors in ATAC, ABCSG 8/ ARNO 95 and IES trial revealed just a benefit in terms of disease-free survival, but not for over-all survival. Thus MA-17 trial is so far the only study which could demonstrate a survival benefit for node positive disease by "extended adjuvant" therapy with letrozole. Node- and receptorpositive, postmenopausal women show a higher benefit by anthracycline containing chemotherapy in combination with tamoxifen, than by endocrine therapy alone. But tamoxifen should given sequentially to chemotherapy (Intergroup 0100/ SWOG-8814 trial). Adjuvant chemotherapy with three cycles FEC followed by three cycles docetaxel reveals a survival benefit compared to six cycles FEC, especially in women older than 50 years (PACS 01 trial). Furthermore there is evolving evidence that dose-dense, interval shortened chemotherapy is superior to standard chemotherapy in adjuvant setting. The impaired survival of receptornegative, nodalpositive breast cancer patients seems to be converted to a survival improvement compared with receptorpositive patients by modern adjuvant cytotoxic regimens (metaanalysis CALGB 8541, 9344, 9741). In primary systemic chemotherapy survival is strongly associated with the rate of pathohistological complete remissions (NSABP B-27). The combination of cytotoxic drugs has no further influence on survival, but the sequential administration of taxane increases the rate of pCR. A difference in survival stratified by pCR and non-pCR in breast and positive nodal status could not be detected, so that the number of involved lymph nodes seems to be the strongest prognostic factor and is independent of tumor response in the breast. The sentinel node biopsy is a safe and reliable method, but the rate of false negative findings depends on the pathohistological methods (NSABP B-32). The morbidity of this method is low compared with conventional axillary dissection in multicenter studies. Local tumor control is an important parameter which offers a significant survival benefit in all age cohorts.

Adjuvant therapy

Concomitant or concurrent systemic cancer therapy Concomitant or concurrent systemic cancer therapy refers to administering medical treatments at the same time as other therapies, such as radiation. Adjuvant hormonal therapy is given after prostate removal in prostate cancer, but there are concerns that the side effects, in particular the cardiovascular ones, may outweigh the risk of recurrence.In breast cancer, adjuvant therapy may consist of chemotherapy (doxorubicin, trastuzumab, paclitaxel, docetaxel, cyclophosphamide, fluorouracil, and methotrexate) and radiotherapy, especially after lumpectomy, and hormonal therapy (tamoxifen, letrozole). Adjuvant therapy in breast cancer is used in stage one and two breast cancer following lumpectomy, and in stage three breast cancer due to lymph node involvement. In glioblastoma multiforme, adjuvant chemoradiotherapy is critical in the case of a completely removed tumor, as with no other therapy, recurrence occurs in 1–3 months.

Eric Winer

Berry DA, Cirrincione C, Henderson IC, et al. Estrogen-Receptor Status and Outcomes of Modern Chemotherapy for Patients with Node-Positive Breast Cancer. JAMA. 2006;295:1658-67. Muss HB, Berry DA, Cirrincione CT, et al. Adjuvant chemotherapy in older women with early-stage breast cancer. New England Journal of Medicine. 2009;360:2055-2065. Sikov WM, Berry DA, Perou CM, et al. Impact of the Addition of Carboplatin and/or Bevacizumab to Neoadjuvant Once-per-Week Paclitaxel Followed by Dose-Dense Doxorubicin and Cyclophosphamide on Pathologic Complete Response Rates in Stage II to III Triple-Negative Breast Cancer: CALGB 40603 (Alliance). Journal of Clinical Oncology. 2015;33:13-21. Tolaney SM, Barry WT, Dang CT, et al. Adjuvant Paclitaxel and Trastuzumab for Node-Negative, HER2-Positive Breast Cancer. New England Journal of Medicine. 2015;372:134-41.

How Often Do Sentinel Lymph Node Biopsy Results Affect Adjuvant Therapy Decisions Among Postmenopausal Women with Early-Stage HR+/HER2- Breast Cancer in the Post-RxPONDER Era?

The RxPONDER trial reported no benefit to chemotherapy among postmenopausal patients with HR<sup+</sup/HER2<sup-</sup tumors, one to three positive nodes, and low recurrence scores, questioning the role of axillary staging in this population. Here, we evaluate the impact of sentinel lymph node biopsy (SLNB) results on adjuvant therapy decisions in postmenopausal women with HR<sup+</sup/HER2<sup-</sup breast cancer. Postmenopausal women with cT1-2N0, HR<sup+</sup/HER2<sup-</sup breast cancer treated with lumpectomy and SLNB from 2012 to 2018 were identified. Receipt of nodal irradiation, indication for axillary lymph node dissection (ALND) and chemotherapy, and partial breast irradiation (PBI) eligibility were reviewed with pre- and post-SLNB results. A total of 1786 women were identified: median age 62 years, 84% with pT1 tumors, and 16% with pT2-3 tumors. Of those, 85% (n = 1525) remained pN0, 14% (n = 244) were pN1, and 1% (n = 17) were pN2-3. A total of 20 (1%) patients had > 2 positive SLNs, necessitating ALND. Pre-SLNB, 1478 women were considered PBI eligible; post-SLNB, 227 (13%) converted to PBI ineligible. In total, 58 patients with positive nodes received nodal irradiation, representing 3% of the entire cohort and 22% of pN+ patients. Overall, 1401 patients had an Oncotype DX recurrence score available, including 1273 patients with pN0 stage and 128 with pN1, with 173 (14%) and 16 (13%), respectively, having a recurrence score > 25, warranting chemotherapy. While few cN0 postmenopausal women with HR<sup+</sup/HER2<sup-</sup tumors had nodal pathology that warranted ALND, receipt of nodal irradiation, or indicated need for chemotherapy, in 13%, SLNB would have an impact on consideration for PBI. Among patients eligible for PBI, findings from SLNB may help refine selection among postmenopausal women with this tumor profile.

InternalMed_Harrison

Data on postmenopausal women are also controversial. The impact of adjuvant chemotherapy is quantitatively less clear-cut than in premenopausal patients, particularly in estrogen receptor– positive cases, although survival advantages have been shown. The first decision is whether chemotherapy or endocrine therapy should be used. While adjuvant endocrine therapy (aromatase inhibitors and tamoxifen) improves survival regardless of axillary lymph node status, the improvement in survival is modest for patients in whom multiple lymph nodes are involved. For this reason, it has been usual to give chemotherapy to postmenopausal patients who have no medical contraindications and who have more than one positive lymph node; hormone therapy is commonly given subsequently. For postmenopausal women for whom systemic therapy is warranted but who have a more favorable prognosis (based more commonly on analysis such as the Oncotype DX methodology), hormone therapy may be used alone. Large clinical

Paget's disease of the breast

Prognosis The presence of three factors for the prognosis has been suggested, whether there is a palpable mass of the disease, whether lymph nodes are positive and whether there is an underlying malignant cancer. If there is none of these, the five- and 10-year survival is 85% and 80% respectively, with adjuvant chemotherapy even 95% and 90%. If there is a palpable mass, it is 32% and 31% respectively, with adjuvant chemotherapy (40% and 35%). Positive lymph-nodes have been positively associated with a palpable mass and affect the prognosis to be now just 28% survival after 10 years (vs 79% without palpable mass and without affected lymph-nodes). Involvement of the lymph nodes does not directly cause any harm, but is merely an indicator of systemic spread.

Estrogen deprivation therapy

Endocrine therapy should not be confused with menopausal hormone therapy or hormone replacement therapy, which is using estrogen and/or progesterone supplements to relieve symptoms of menopause. Estrogen feeds breast cancer cells, so when a woman on hormone replacement therapy (HRT) is diagnosed with ER/PR positive breast cancer, her doctor will ask her to stop the HRT. Patients that have tumors small enough to take out with surgery will receive endocrine therapy after their surgery, which is part of adjuvant therapy. Large tumors may receive neo-adjuvant therapy via chemotherapy or radiation to shrink the tumor small enough to operate on. Types of Endocrine Therapy Medication

Adjuvant therapy

Despite the initial pushback from the breast cancer surgeons who believed that their radical mastectomies were sufficient in removing all traces of cancer, the success of Bonadonna's and Fisher's trials brought adjuvant therapy to the mainstream in oncology. Since then, the field of adjuvant therapy has greatly expanded to include a wide range of adjuvant therapies to include chemotherapy, immunotherapy, hormone therapy, and radiation. Neoadjuvant therapy Neoadjuvant therapy, in contrast to adjuvant therapy, is given before the main treatment. For example, systemic therapy for breast cancer that is given before removal of a breast is considered neoadjuvant chemotherapy. The most common reason for neoadjuvant therapy for cancer is to reduce the size of the tumor so as to facilitate more effective surgery.

Breast cancer

Medication Medications used after and in addition to surgery are called adjuvant therapy. Chemotherapy or other types of therapy prior to surgery are called neoadjuvant therapy. Aspirin may reduce mortality from breast cancer when used with other treatments. There are currently three main groups of medications used for adjuvant breast cancer treatment: hormone-blocking agents, chemotherapy, and monoclonal antibodies.

[Adjuvant chemotherapy in primary carcinoma of the breast].

The 2003 St. Gallen consensus on primary therapy of early breast cancer confirmed the importance of adjuvant chemotherapy. In endocrine non-responsive tumors, chemotherapy is adjuvant treatment of choice, independent of patient age or lymph node status. In endocrine-responsive disease, chemotherapy plays an important role next to endocrine treatment. The questions, which patients need combined chemo-endocrine therapy, and for whom endocrine therapy alone is sufficient, are still unsolved. Anthracyclines are standard adjuvant chemotherapy; superiority over CMF has only been shown for anthracyclin-containing polychemotherapy with at least 3 substances. Recent published evidence suggest that adding taxanes to anthracyclin regimens may benefit patient survival and that taxanes are a valid therapeutic option in node-positive, hormone receptor negative breast cancer. The optimal use of taxanes in different risk collectives is currently being investigated in clinical trials. Generally, adjuvant chemotherapy should be administered before radiotherapy, and endocrine therapy should be given sequentially. In view of the international St. Gallen panel, the final publication may only represent a minimal consensus. Individual countries are requested to adapt these recommendations to national conditions. In Germany, up-to-date evidence-based therapy recommendations have just been issued by the AGO "breast" expert panel. Interdisciplinary S3 breast cancer guidelines are currently being finalized.

[Results of 10 years of a randomized trial of neoadjuvant chemotherapy in breast cancers larger than 3 cm].

The aim of this randomised trial was to determine advantages and drawbacks of neo-adjuvant chemotherapy in patients with operable breast cancers > 3 cm. Two hundred and seventy-two women (age 70) with operable breast cancers larger than 3 cm (T2-3/N0-1/M0) were included in a randomised trial from January 1, 1985 to April 30, 1989. Patients in group A (n = 138) were treated by mastectomy and axillary node dissection. Adjuvant chemotherapy was indicated for 104 patients with axillary node involvement (n = 82) or negative oestrogen and progesterone receptors (EPR-) (n = 22). Patients in group B (n = 134) were treated by initial chemotherapy (identical as in group A) followed by locoregional treatment according to the response. Before treatment, the average of clinical tumoural diameter was 43 mm. The median follow-up was 124 months. In group B, 49 patients (36.5%) were resistant to chemotherapy; a conservative breast surgical treatment was performed in the other 84 patients sensitive to chemotherapy (62.6%). In this last subgroup, 19 (22.6%) needed a secondary mastectomy because of locoregional recurrence. Survival rates were not different in groups A and B, but loco-regional recurrences were frequent in group B. At 10 years, the overall survival rate was 60% and half of living patients in group B were free of cancer and with their breast. Neoadjuvant chemotherapy permitted in two-thirds of cases breast conservation treatment, initially considered to be impossible. Locoregional recurrences are more frequent than after mastectomy and adjuvant chemotherapy.

[Effectiveness of adjuvant systemic therapy in organ preserving treatment of pT1-2N0M0 breast cancer].

Randomized study was made of 317 patients with early stages (pT1-2N0M0, tumor size of 0.1-3.0 cm in diameter) of infiltrative duct breast cancer, underwent an organ sparing treatment (sectorial resection +/- axillary dissection) either in combination with adjuvant chemotherapy or hormone therapy with tamoxifen or without them. It was shown that probability of recurrence development (in residual breast and regional nodes) was practically similar in women underwent organ sparing treatment if tumor size was not more than 3 cm. It was also found that prescription of adjuvant chemotherapy or hormone therapy with tamoxifen as additional to surgical treatment of tumors within the range from 0.1 to 3.0 cm in diameter did not result in significant reduction in local and regional relapses.

[Breast cancer: adjuvant hormone and chemotherapy].

Indications and types of adjuvant treatment depend on the number of infiltrated axillary lymph nodes, menopausal and hormonal receptor status. In N0 situation is to date no indication for hormonal or cytotoxic therapy outside of clinical trials: disease-free survival may be improved but overall survival is not influenced. In N+ situation premenopausal patients should receive polychemotherapy independent from hormonal receptor status, postmenopausal patients with positive receptor status should be treated with tamoxifen up to 5 years: in this situation disease-free interval and overall survival can be enhanced significantly.

Breast cancer classification

Receptor status is a critical assessment for all breast cancers as it determines the suitability of using targeted treatments such as tamoxifen and or trastuzumab. These treatments are now some of the most effective adjuvant treatments of breast cancer. Estrogen receptor positive (ER+) cancer cells depend on estrogen for their growth, so they can be treated with drugs to reduce either the effect of estrogen (e.g. tamoxifen) or the actual level of estrogen (e.g. aromatase inhibitors), and generally have a better prognosis. Generally, prior to modern treatments, HER+ had a worse prognosis, however HER2+ cancer cells respond to drugs such as the monoclonal antibody, trastuzumab, (in combination with conventional chemotherapy) and this has improved the prognosis significantly. Conversely, triple negative cancer (i.e. no positive receptors), lacking targeted treatments, now has a comparatively poor prognosis.

Adjuvant therapy of primary breast cancer: a review of key findings from the 7th international conference, St. Gallen, February 2001.

Breast cancer research has developed at a rapid pace over the last decades. Recent discoveries promise to provide individualized treatment options, increased long-term survival for women with breast cancer, and the possibility of moving toward curative intent in the treatment of advanced breast cancer. Age, race, tumor size, histological tumor type, axillary nodal status, standardized pathological grade, and hormone-receptor status are accepted as established prognostic and/or predictive factors for selection of systemic adjuvant treatment of breast cancer. The role of other promising new factors, such as p53 mutations, HER-2 status, plasminogen activator system, histological evidence of vascular invasion, and quantitative parameters of angiogenesis will be determined in ongoing prospective studies. Currently, 5 years' treatment with adjuvant tamoxifen in women with hormone-positive receptor status, is regarded as the optimal duration of treatment. Long-term follow-up on the randomized trials will determine the added benefit of treatment beyond 5 years. Ovarian ablation has shown a reduction in recurrence and death, and the exact role and extent of adjuvant chemotherapy in premenopausal women with hormone-responsive tumors is under discussion. Combination hormonal and chemo-hormonal therapies are also being evaluated. There are no convincing data on the survival impact of tamoxifen as a preventative therapy for breast cancer: longer-term follow-up is required, and the planned meta-analyses in 2005 should help shed light on this issue. Statistically significant benefits have been observed with adjuvant chemotherapy (particularly with anthracycline-containing regimens in premenopausal women) versus no adjuvant chemotherapy. The optimal length of adjuvant anthracycline/cyclophosphamide (AC) regimens needs further evaluation as do randomized comparisons of AC to cyclophosphamide/ doxorubicin/5-fluorouracil (5-FU) and cyclophosphamide/epirubicin/5-FU. Although taxanes promise to provide an additive benefit to adjuvant chemotherapy regimens, the Cancer and Leukemia Group B 9344 and the National Surgical Adjuvant Breast and Bowel Project B-28 studies evaluating paclitaxel in the adjuvant setting have not yet demonstrated statistically significant benefits on disease-free survival and overall survival. In the year 2000, all adjuvant therapy studies conducted by the Co-operative Groups in both node-negative and node-positive disease involve a taxane. High-dose chemotherapy evaluations are still ongoing. The numerous prospective adjuvant therapy trials (hormonal; selective estrogen-receptor modulators; aromatase inhibitors; chemotherapy, involving anthracyclines/taxanes/platinum/trastuzumab; biological factors; elderly women (>70 years); high-risk patients; radiotherapy in 1-3 positive lymph nodes), and neoadjuvant studies might further define the chances to enhance cure rates in the treatment of primary breast cancer.

[Differences in Treatment Effect between Local and Distant Lesions in Breast Cancer Patients Administered Neoadjuvant Endocrine TherapyGuided byOncoty pe DX-A Case Report].

We report different treatment effects between local and distant lesions based on oncotype DX in a patient with breast cancer administered neoadjuvant endocrine therapy. The patient was a 50-year-old woman. Ultrasound(US)showed a mass 16×11×11mm in diameter in the C area of her right breast. Histological examination revealed invasive ductal carcinoma positive for estrogen and progesterone receptor and negative for human epidermal growth factor receptor type 2(HER2), and a Ki-67 index of 38%. The recurrence score(RS)calculated from the core needle biopsy was 4(low-risk group)with a predicted 10-year risk of distant recurrence of 4% after 5 years of endocrine therapy. Oncotype DX showed that this patient would not benefit from chemotherapy. We administered neoadjuvant endocrine therapy. However, the tumor size increased to 26×18×15mm 1 month after treatment initiation. Therefore, right breast-conserving surgery and sentinel lymph node biopsy were performed. Histopathologically, the effect of the endocrine therapy was grade 0 and the surgical margins were negative. Even though RS was low in the breast, the effect of endocrine therapy differed between local and distant lesions such as circulating tumor cells.

[The importance of the extracapsular extension of the sentinel node metastasis in the surgical treatment of breast cancer].

Introduction: The introduction of sentinel node biopsy (SNB) has led to a significant decrease of axillary lymph node dissections (ALND). The importance of the extracapsular extension (ECE) in the sentinel lymph node (SN) remains unclear. Method: The data of 635 patients with T1-T2N0M0 invasive breast cancer who underwent SNB between 2014 and 2018 were retrospectively analysed. 25% of the SNB patients (158) had metastasis in the SNs. These patients were grouped based on the presence or absence of ECE. The main objective of our study was to analyse the occurrence of massive (>3) node metastasis in the case of ECE negative and ECE positive patients, where ALND was performed. Results: There were 91/158 patients (58%) in the ECE negative group and 67/158 patients (42%) in the ECE positive group. ALND was performed in 42% of the ECE negative and in 69% of the ECE positive patients. There were no significant differences in the mean age of the patients; size, histological type and grade of the tumours, presence of lymphovascular invasion and proportion of hormone and HER2 receptor positivities. In the ECE negative ALND group, pN1 involvement was 82%, pN2+pN3 involvement represented 18% of cases. In the ECE positive ALND group, pN1 involvement was 60%, pN2+pN3 involvement was found in 40% of cases. The presence of ECE was associated with greater axillary disease burden. These results show a significant difference (<ip</i = 0.038). Conclusions: ECE of the SN is an important predictor for non-sentinel lymph node involvement. These data suggest, when ECE is confirmed, it is a further factor to be considered in deciding about ALND.

Strategies in treating male breast cancer.

Male breast cancer is rare. Median age at diagnosis is approximately 65 years, and > 35% of male breast cancers occur in elderly men. Retroareolar lump is the most frequent symptom, and 25-30% of tumours are T(4) lesions. Infiltrating ductal carcinoma represents almost 90% of the cases, and 10% are ductal carcinoma in situ. Axillary nodal involvement is present in 50-60% of the cases. Estrogen and progesterone receptors are positive in 75-92% and 54-77% of the cases. Mastectomy with axillary dissection remains the standard treatment. Sentinel lymph node biopsy could be proposed in small tumours (< or = 2 cm). Locoregional radiotherapy is very often indicated. Tamoxifen is the standard adjuvant treatment, but chemotherapy is proposed in young men with axillary nodal involvement and/or negative hormone receptors. Tumour size and, more particularly, histopathological axillary involvement are the strongest predictive factors for both locoregional recurrence and metastasis. Globally, the prognosis is similar to that in women (at identical stage), but the intercurrent death rate is higher due to the important impact of comorbidities and second neoplasm.

Neoadjuvant Chemotherapy with Docetaxel, Carboplatin and Weekly Trastuzumab Is Active in HER2-Positive Early Breast Cancer: Results after a Median Follow-Up of over 4 Years.

Most patients with HER2-positive breast cancer receive chemotherapy and trastuzumab. Data from adjuvant trials have shown that the combination of docetaxel, carboplatin and weekly trastuzumab (TCH) is well tolerated and as effective as anthracycline-containing regimes. Previous investigations on neoadjuvant treatment with taxanes, platinum salts and trastuzumab showed pathological complete remission (pCR) rates between 43.3 and 76%. To date, the longest published follow-up in this indication is 3 years. Here we present 4-year follow-up data for a cohort of 78 patients treated with neoadjuvant TCH. Between 2009 and 2014 we treated 78 patients with operable HER2-positive breast cancer with a neoadjuvant schedule of docetaxel (75 mg/m<sup2</sup) and carboplatin (AUC 6) every 3 weeks (q3w) and trastuzumab (4 mg/kg loading dose then 2 mg/kg) q1w. Lymph node involvement was verified by sentinel lymph node or core-cut biopsy. Patients were diagnosed at a mean age of 55.5 years; 65.4% had hormone receptor-positive tumors, 34.6% presented with grade 3 disease and 51.3% of patients were node positive. Patients were monitored every 2 cycles by ultrasound. After 6 cycles of chemotherapy all patients had surgery. Axillary dissection was performed in case of positive lymph node status prior to TCH. After surgery, trastuzumab was continued q3w up to 1 year. No grade III/IV toxicities occurred and no case of congestive heart failure was observed. Neither dose modifications nor dose delays were necessary. 34 of the 78 patients (43.6%) achieved a pCR, 27 of the 40 node-positive patients (67.5%) experienced nodal conversion. After a median follow up of 48.5 months the disease-free survival (DFS) was 84.6%, the distant disease-free survival (DDFS) was 87.2% and the overall survival (OS) was 91%. Only T stage and nodal status at baseline were found to be significantly associated with survival estimates. The anthracycline-free regimen TCH is effective and safe in the neoadjuvant therapy of HER2-positive breast cancer, yielding DFS, DDFS and OS probabilities comparable to the results of adjuvant trials. Our data support the use of TCH as a neoadjuvant therapy regimen for patients with HER2-positive breast cancer. They also strongly encourage the use of taxanes and platinum salts as the chemotherapy backbone in studies investigating dual blockade with trastuzumab and pertuzumab in the neoadjuvant setting.

Adjuvant chemotherapy for elderly patients (> or =70 years) with early high-risk breast cancer: a retrospective analysis of 260 patients.

Adjuvant chemotherapy in elderly women is currently perceived as one of the priorities in breast cancer (BC) research and, to date, we lack practical guidelines in this age group. Therefore we performed a retrospective analysis of the actual use of adjuvant chemotherapy according to each negative prognostic factor. Charts of all consecutive elderly patients aged 70 years or more with operable BC referred to our institution between 1999 and 2003 were reviewed for tumour stage and treatment, and compared with an equal cohort of younger randomly selected postmenopausal patients (control group). A total of 260 elderly patients (mean age 75.6 years, age range 70-97 years) with histological diagnosis of early BC were eligible. Conserving surgery was performed in 54.6% of patients, nodal dissection in 84.6% and sentinel node biopsy in 5.8%. Tumour size was pT2-pT3 in 45.4% of patients; grading was G3 in 27.3%, hormonal status was negative (HR-) in 16.9% and lymph nodes were involved N+ in 36.1%. Of 188 patients presenting one or more risk factors (pT2-3, G3, N+, HR-), 48.4% were not proposed for adjuvant chemotherapy (compared with 7.2% in the control group), 39.8% of those with nodal involvement (compared with 4.3% of controls, P <0.0001) and 22.7% of those who were HR- (compared with 0.0% of controls, P=0.0002). Considering only patients receiving non-anthracycline-based chemotherapy, 20 elderly patients (25.9%) were unable to complete the planned number of cycles (compared with 4.7% of controls, P=0.0002). The 2-year disease-free survival was significantly decreased in N+ HR- patients compared with the remaining elderly patients (49.9% compared with 90.9%, P=0.0006). Elderly BC patients receive much less adjuvant chemotherapy, according to each prognostic factor. N+ HR- disease probably represents the most reasonable indication. As the toxicity of the CMF regimen frequently caused interruption of treatment, alternative regimens should be assessed in this age class.


Absences behave as brief episodes of abrupt loss of consciousness without alteration of postural control; they typically last seconds and can be repeated many times a day, are usually accompanied by small bilateral motor signs (blinking, chewing) and consciousness is recovered equally abruptly, without subsequent confusion or memory of the episode (MIR 03-04, 248; MIR 97-98, 51). The age of onset is usually between 4 years and early adolescence, being the most frequent cause of seizures in this age range. EEG findings are typically generalized and symmetrical spike-wave discharges at 3 Hz (MIR 99-00F, 67) coinciding with seizures, although in the interictal EEG there are more periods of abnormal activity than clinically visible. The most appropriate drugs for the treatment of absences are Valproate and Ethosuximide (CTO Manual).

A 10-year-old boy with brief episodes of distractibility (< 1 minute) in which he does not respond to calls and blinks. An EEG shows spike-wave discharges at 3 cycles per second. First-line elective treatment would be with:

[Electroencephalography in status epilepticus in sleep (ESES) in various clinical pictures].

Electroencephalographic epileptic status during sleep (ESES--according to Electrical Status Epilepticus in Sleep) is characterized with paroxysmal attacks of 1.5-3.5 (even to 5) Hz/s spikes and waves during NREM. A case is presented of a 7-year-old boy who had normal development until 3 years of age when epileptic attacks started. First to appear were left-sided, hemifacial twitches with orofacio-lingual deficits. Despite treatment with various types and combinations of antiepileptic medications, the attacks persisted and became more frequent. About a year after the onset of the disease, the spectrum of epileptic attacks had expanded (left-sided tonic-clonic, atonic-astatic, myoclonic, atypical absences, and then drop attacks and negative myoclonic seizures became dominant). The boy appeared mentally retarded. During the course of the disease, the diagnoses varied: hemifacial twitches, partial epilepsy, left-sided partial epilepsy, atypical benign epilepsy, Landau-Kleffner syndrome, myoclonic-astatic epilepsy. A year and a half after the onset of the disease EEG (polysomnographic whole-night recording) revealed electrical status epilepticus in sleep (ESES) with spike-wave index > 85%. It appeared that this was continuous spike and wave during slow wave sleep syndrome (CSWS) with characteristic attacks, bifrontal atrophies on brain CT and right frontotemporal EEG focus. Treatment with valproate and ethosuximide combined with vigabatrin and clonazepam seemed to be effective. In the last 20 months ESES is rare and transitory, mental and neuropsychological functions have improved, but he still has several hemifacial twitches daily. The two brain MRI scans were normal. Differential diagnosis can be atypical benign epilepsy (suspected familial diagnosis). Family history of atopy, 'persistent' colds and obstructive bronchitis in the boy and treatment with antiepileptic medications (especially carbamazepine, phenobarbital and phenytoin) could have been provoking or modulating factors of the epileptic disease. So far we have not identified an epileptic syndrome because it seems that multiple clinical pictures overlap. ESES could be diagnosed using polysomnographic whole-night recording with calculated spike-wave index. Follow-up of the spike-wave index could be useful in differentiation, but not in precise diagnosis of epileptic syndrome. Clinical course could be modulated by different factors. Continuous following over a long period could be helpful in the classification of epilepsy.

First_Aid_Step2

EEG typically shows 10-Hz activity during the tonic phase and slow waves during the clonic phase. Protect the airway. Treat the underlying cause if known. 1° generalized tonic-clonic seizures: Phenytoin, fosphenytoin, or valproate constitutes first-line therapy. Lamotrigine or topiramate may be used as adjunctive therapy. Secondarily generalized tonic-clonic seizures: Treatment is the same as that for partial seizures. Begin in childhood; subside before adulthood. Often familial. Hx/PE: Present with brief (5to 10-second), often unnoticeable episodes of impaired consciousness occurring up to hundreds of times per day. Patients are amnestic during and immediately after seizures and may appear to be daydreaming or staring. Eye ﬂuttering or lip smacking is common. Dx: EEG shows classic three-per-second spike-and-wave discharges. Tx: Ethosuximide is the first-line agent.

Perioral myoclonia with absence seizures: a rare epileptic syndrome.

We present the clinical and video-EEG data on an epileptic boy whose absence seizures with marked perioral movements had started at the age of 1.5 years. From age 12 years, he experienced frequent episodes of typical absence status epilepticus (ASE) lasting 1-2 hours with marked perioral myoclonia and moderate confusion. Initial therapy with carbamazepine was substituted by valproate because of worsening of the absence seizures. At the age of 17, the patient was admitted to our clinic with his usual, but long lasting ASE attack, accompanied by 2 generalized tonic-clonic convulsions. ASE was confirmed with the EEG which showed continuous 3 Hz spike and wave paroxysms with occasional normal intervals of 1-5 seconds. IV injection of clonazepam improved the clinical and EEG findings immediately. Video- EEG examination performed after a few weeks demonstrated typical absence seizures with perioral myoclonia. Based on the characteristics of seizure semiology, other clinical data and EEG findings, the patient was diagnosed as having the syndrome of "perioral myoclonia with absence seizures" described by Panayiotopoulos.

[A late-onset case of nonconvulsive status epilepticus of generalized epilepsy].

We report a 78-year-old woman who had episodes of nonconvulsive status epilepticus (NCSE) with dizziness. At 75 years of age, she had first seizure, but was not well examined. At 78 years of age, she had brief myoclonic jerks of her arms, soon after awakening, in May. She suffered from strong dizziness and was admitted in our hospital at the end of June. The symptoms regressed with bed rest in few days and she was discharged. However, she was admitted again with dizziness in the middle of July. There were no myoclonic jerks of her arms or legs and she could converse and interact normally, but was slightly disoriented (JCS: 2). Blood test, Cerebrospinal fluid analyses and brain MRI were normal. An EEG showed frequent intermittent generalized multiple spikes and slow wave complexes and a 3-4 Hz generalized spike and slow wave complexes every 2-4 seconds during whole 20 minutes record. Intravenous injection of 5 mg diazepam terminated status immediately. Thereafter, she was treated with sodium valproate (400 mg/day). Her symptoms improved, and interictal epileptic discharges extremely decreased. Late-onset NCSE of generalized epilepsy is rare. We discussed this case as an important case for diagnosis of NCSE with subtle symptom of dizziness.

Epileptic negative myoclonus induced by carbamazepine in a child with BECTS. Benign childhood epilepsy with centrotemporal spikes.

A 7-year-old female with benign childhood epilepsy with centrotemporal spikes developed epileptic negative myoclonus (ENM) seizures during carbamazepine (CBZ) treatment. She had experienced nocturnal partial seizures since 5 years of age. Interictal electroencephalography demonstrated typical rolandic discharges. Valproate was first initiated at 6 years of age, but the seizures were uncontrollable. Carbamazepine was added and valproate withdrawn. The frequency of partial seizures did not decrease. Moreover, she had brief episodes of tone loss in each or both arms and eye blinking several weeks after CBZ introduction. Unilateral loss of arm tone corresponded to spike-and-wave discharges in the contralateral centrotemporal region, and a loss of tone in arms was associated with bilateral synchronous discharges. Eye blinking was also related to bilateral synchronous discharges and classified as a myoclonic seizure. The ENM and myoclonic seizures disappeared soon after CBZ withdrawal. Therefore the authors concluded that CBZ induced the ENM and myoclonic seizures in this patient. CBZ sometimes induces generalized seizures in the treatment of partial epilepsy and generalized epilepsy. CBZ-induced ENM seizures should be considered when a brief lapse of tone appears during CBZ treatment.

Effects of clonazepam on self-induced photoparoxysmal responses.

A 5-year-old girl exhibited daily episodes of repetitive blinking lasting 5-10 s. Electroencephalography (EEG) revealed marked photoparoxysmal responses (PPR) at 3-20 Hz of photic stimulation and diffuse spike-wave bursts during sleep. A 24-h video EEG identified 11 episodes of repetitive blinking, 3 of which resulted in widespread spike-wave discharges. These suggested that the behavior of the patient represented self-induction of PPR. Valproate sodium was ineffective in decreasing PPR, as revealed by EEG, and the frequency of blinking episodes, but clonazepam attenuated PPR and significantly decreased the blinking behavior.

Somnambulism in adults.

We evaluated with clinical interviews and polysomnographic examinations 10 adults with the complaint of sleepwalking, often accompanied by violent behavior or self-injury. During the polysomnographic studies, 8 patients had 47 distinct somnambulistic episodes. All episodes occurred in non-REM sleep, with 91% occurring in slow-wave sleep. Contrary to previous reports, episodes were not confined to the 1st 3rd of the night. Clinical EEGs were normal in 5 of 6 patients. In the 7 patients tried on 1 or more treatment regimens, clonazepam effectively suppressed the somnambulism in 5 of 6 patients in whom it was tried, carbamazepine in 1 of 3, flurazepam in 2 of 2, and a combination of clonazepam and phenytoin in one.

Gabapentin: new indication. Little impact on partial epilepsy in children between 3 and 12.

(1) The standard treatment for partial epilepsy in children is carbamazepine. The efficacy of other antiepileptics has also been documented, either alone (phenobarbital, oxcarbazepine, valproate sodium, phenytoin), or in drug combinations (lamotrigine, topiramate). (2) A licence extension has been granted in France for gabapentin in partial epilepsy in children aged 3 to 12 years, in combination with other antiepileptics. (3) The clinical file contains no data from trials comparing gabapentin with other antiepileptics. (4) The main double-blind trial involved 247 children who were treated either with their usual treatment + gabapentin or usual treatment + placebo. Gabapentin was only moderately effective, and the overall number of responders did not differ significantly between the gabapentin and placebo groups. (5) In this trial the main adverse effects among the children on their usual treatment + gabapentin were behavioural disorders (hostility and mood swings). (6) In practice, the licensing of gabapentin for children with partial epilepsy aged between 3 and 12 years changes nothing in their practical management.

[Chronological change of EEG findings in a case of pyridoxine dependency seizures].

A patient of pyridoxine dependent seizures was reported. He was born at 34 weeks' gestation and weighted 2,760 g. Apgar scores were 6 and 9 at 1 and 5 minutes, respectively. He showed the first seizure 2 hours after his birth. Phenobarbital, phenytoin, sodium valproate, diazepam and clonazepam were not effective. Pyridoxal phosphate (50 mg) was given intravenously, resulting in suppression of convulsions. However, muscle tonus was severely depressed. In EEG, a discontinuous pattern was found in quiet and indeterminate sleep on the 2nd day of life. At 5th week multifocal spikes were found, and the discontinuous pattern persisted. Ictal discharges at 13th week showed generalized, continuous, irregular and high voltage slow waves with multifocal spikes. At 27th week of life, high voltage slow waves disappeared and multifocal spike discharges decreased. At 2 years and 10 months of age, the patient was suffering from athetotic cerebral palsy and severe mental retardation. Pyridoxal phosphate at the doses of 35-40 mg/kg/day had been administered. Irritability sometimes occurred and additional 50 mg of pyridoxal phosphate controlled this irritability effectively.

Rolandic epilepsy

Treatment Given the benign nature of the condition and the low seizure frequency, treatment is often unnecessary. If treatment is warranted or preferred by the child and his or her family, antiepileptic drugs can usually control the seizures easily. Carbamazepine is the most frequently used first-line drug, but many other antiepileptic drugs, including valproate, phenytoin, gabapentin, levetiracetam and sultiame have been found effective as well. Bedtime dosing is advised by some. Treatment can be short and drugs can almost certainly be discontinued after two years without seizures and with normal EEG findings, perhaps even earlier. Parental education about Rolandic epilepsy is the cornerstone of correct management. The traumatizing, sometimes long-lasting effect on parents is significant. It is unclear if there are any benefits to clobazam over other seizure medications.

[Idiopathic generalised epilepsies in the elderly: the viewpoint of a geriatrician].

Long-term follow-up studies indicate a low remission rate in idiopathic generalised epilepsies (IGE) (Martinez-Juarez et al., 2006), suggesting they may persist to an advanced age. However there are few estimates of IGE frequency in the elderly. EEGs of 700 patients aged over 70 years, recorded between January 2006 and March 2007, were reviewed for anomalies consistent with IGE. We then examined the clinical history of patients with these anomalies. A persistent IGE was identified in four female patients (mean age: 79 years); in two cases it was a juvenile myoclonic epilepsy (JME) and in two an epilepsy with grand mal seizures. Seizures in three patients had begun in childhood or adolescence and in one at 40 years. Before hospitalization, few or no seizures were reported and IGE had not been diagnosed. IGE was revealed in each patient by a relatively severe event: an absence status (AS), subcontinuous myoclonic seizures or repeated convulsive generalised seizures (CGS). These events were not situation-related but in one patient the relapse of simple convulsive seizures, may have been related to the withdrawal of anti-epileptic drugs (AED) several months previously. EEG records showed generalised spikes or polyspikes and waves organised in a status epilepticus or in interictal rhythmic discharges. In one case they were evident only from a 24 hours recording. Clonazepam injection was used to suppress the AS episode and the subintrant myoclonia. After the AS, interictal generalised epileptic discharges persisted. Two of the four patients had familial history of epilepsy or febrile seizures but in no case was an epileptogenic lesion evident in brain CT scan or MRI. Clinical exams and biologic parameters were normal. All of the patients had worked and were married with children. Appropriate therapies were followed after the diagnosis of IGE. One patient with JME had been treated by Valproate which was discontinued by the general practitioner because of lethargy and replaced by Carbamazepine; seizures were aggravated under both Carbamazepine and then Lamotrigine and until the patient became seizure-free on Levetiracetam. The antiepiletic treatment was also modified in a second patient, while the two others responded well to Valproate. IGE can exacerbate in the elderly, as different types of seizures including AS, subintrant myoclonia or repeated CGS. Our data suggest persistent IGE are quite frequent in an aged population and may be underestimated due to difficulties in diagnosis. Correctly diagnosed, adjustment of AED may offer substantial clinical improvements in IGE of the elderly.

[Clinical and electroencephalographic characteristics of epilepsy with myoclonic absences].

Epilepsy with myoclonic absences (EMA) is a type of childhood epilepsy characterized by a specific seizure type, i.e. myoclonic absences (MA). This study aimed to investigate the clinical and electrophysiological characteristics of EMA. Video-EEG monitoring was carried out in 6 patients with EMA, and 2 of them were examined with simultaneous deltoid muscle surface electromyogram (EMG). The clinical and EEG characteristics, treatment and prognoses of EMA were analyzed. Of the 6 patients, 3 were female, and 3 were male. The age of onset was from 2 years and 3 months to 11 years (average 5 years and 2 months). MA was the sole seizure type in 5 patients. One patient presented generalized tonic clonic seizures (GTCS) at the onset and then switched to MA. The manifestations of MA included an impairment of consciousness of variable intensity, rhythmic myoclonic jerks with evident tonic contraction mainly involving the upper extremities, a deviation of head and body to one side or asymmetrical jerks observed in some cases, a duration ranging from 2 to 30 s, an abrupt onset and termination, a high frequency of attacks, at least several times to over 30 times per day, and easily provoked by hyperventilation. The ictal EEG consisted of rhythmic 3 Hz spike and wave discharges that were bilateral, synchronous and symmetrical in all patients. The deltoid muscle EMG recording in 2 patients showed rhythmic myoclonus at the same frequency as the spike and waves. The interictal EEG showed generalized spike and wave discharges in all patients, and focal discharges in some patients. Valproate was the drug of choice, which was often combined with other antiepileptic drugs. The ages at follow up ranged from 6 years and 4 months to 19 years. Seizures were controlled from 8 months to 3 years in 4 cases. The treatment at the onset was late in one case and was irregular in another who had GTCS during the course of the disease. These two cases were followed up for 2 years and 6 months and 5 years, respectively. Seizures could not be controlled in the 2 patients with intellectual impairment. EMA was a rare type of childhood epilepsy characterized by MA. Clinical observation and ictal video-EEG and EMG were essential to diagnose EMA. Valproate alone or combined with other antiepileptic drugs given early could have a favorable effect to EMA. Delayed therapy and the presence of GTCS might suggest poor prognosis.

Neurology_Adams

Carbamazepine is effective in 70 to 80 percent of patients (600 to 1,200 mg/d), but half become tolerant over a period of several years. Other antiepileptic drugs such as phenytoin (300 to 400 mg/d), valproic acid (800 to 1,200 mg/d), clonazepam (2 to 6 mg/d), gabapentin (300 to 900 mg/d or more), pregabalin (150 to 300 mg/d), and carbamazepine in combination with other medications, suppress or shorten the duration and severity of the attacks in most patients for varying times. Baclofen may be useful in patients who cannot tolerate carbamazepine or gabapentin, but it is most effective as an adjunct to one of the anticonvulsant drugs. Capsaicin applied locally to the trigger zones or the topical instillation in the eye of an anesthetic has been helpful in some patients. By temporizing and using these drugs, one may permit a spontaneous remission to occur in perhaps 1 in 5 patients over a year or two.

Jeavons syndrome

Management Based on anecdotal evidence, the drugs of choice are those used for other idiopathic generalized epilepsies. Valproate alone, or most probably in combination with clonazepam, levetiracetam, lamotrigine or ethosuximide, appears to be the most effective regimen. The choice of the second drug depends on the main seizure type. Clonazepam is highly efficacious in eyelid myoclonia and myoclonic jerks. Of the newer antiepileptic drugs, levetiracetam may be the most effective, because of its anti myoclonic and anti photosensitive properties. Lamotrigine is very effective in absence seizures but may exaggerate myoclonic jerks. Contra-indicated drugs are: Carbamazepine, gabapentin, oxcarbazepine, phenytoin, pregabalin, tiagabine and vigabatrin.

Panayiotopoulos syndrome

At the age of 2 years, a girl had an autonomic status epilepticus during sleep. This was characterized by pallor, progressive impairment of consciousness, and vomiting that lasted 45 minutes. A second episode occurred after 11 months, during sleep, and consisted of impairment of consciousness, hypotonia, deviation of the eyes to the right, hypersalivation, and right-sided clonic convulsions. It was terminated after 45 minutes with rectal diazepam. Treatment with carbamazepine was initiated. After 6 months, she had a third episode similar to the previous ones, but shorter. At the age of 4 years 9 months, during an ambulatory EEG, she had another autonomic seizure with marked ictal EEG abnormalities, but again, the interictal did not show any spikes. Carbamazepine was replaced with phenobarbital. All 12 interictal EEGs during the active seizure period, 6 of them during sleep, were normal. At last follow-up at the age of 16 years, she was well, a good student, unmedicated, and

Exacerbation of seizures in children by carbamazepine.

We studied 15 children with complex partial seizures in whom one or more seizure type was exacerbated during treatment with carbamazepine. The most common seizure type that was exacerbated was generalized atypical absence (11 patients). Four patients had more frequent and severe generalized convulsive seizures. Monitoring with video-electroencephalographic telemetry suggested that the electroencephalogram can be used to predict the risk of seizure exacerbation with carbamazepine. A bilaterally synchronous spike-and-wave discharge of 2.5 to 3 cycles per second is predictive of increased atypical absence seizures with carbamazepine, whereas generalized bursts of spikes and slow waves of 1 to 2 cycles per second suggest a risk of increased generalized convulsive seizures. Carbamazepine should be used with caution in children with a mixed seizure disorder, particularly those with a generalized bilaterally synchronous discharge of 2.5 to 3 cycles per second on the electroencephalogram. The drug should be considered a possible precipitating factor in any child with an increased frequency of generalized convulsive or generalized absence seizures concomitant with administration of this anticonvulsant agent.

The effectiveness of clonazepam on the Rolandic discharges.

Rolandic discharge (RD), noted in the electroencephalography (EEG) of patients with benign epilepsy in childhood with centrotemporal spikes (BECCT) has several unique features. One feature is that the amount or frequency of RDs does not correlate well with the incidence of seizures in BECCT although it is a key finding in the diagnosis of this epileptic syndrome. In this study, we examined the efficacy of antiepileptic drugs focusing on the disappearance of RDs in relationship with seizure control. Forty patients with BECCT who were not medically treated prior to this study were randomly sorted into three groups. Twenty patients were assigned for clonazepam (CZP) treatment, 10 patients for valproate (VPA) and the remaining 10 patients for carbamazepine (CBZ). Each drug was administered for 4 consecutive weeks. EEGs were recorded twice during the study, before and 4 weeks after the medication trial. The effects of each treatment on RDs were assessed. RDs disappeared in 15 of the 20 cases treated with CZP (75%) within 4 weeks while the same was observed in only one of the 10 cases treated with VPA (10%). CBZ failed to demonstrate any effect on RD. In the group treated with CZP, there were no differences in seizure incidence, seizure type and blood concentration of CZP between the patients whose RDs disappeared and those whose RDs remained.

Hypomania

Treatment Medications Antimanic drugs are used to control acute attacks and prevent recurring episodes of hypomania combined with a range of psychological therapies. The recommended length of treatment ranges from 2 years to 5 years. Anti-depressants may also be required for existing treatments but are avoided in patients who have had a recent history with hypomania. Sertraline has often been debated to have side effects that can trigger hypomania. These include antipsychotics such as: Aripiprazole Clozapine Haloperidol Olanzapine Paliperidone Quetiapine Risperidone Ziprasidone Other anti-manic drugs that are not antipsychotics include: Carbamazepine Lithium Oxcarbazepine Valproate Benzodiazepines such as clonazepam or lorazepam may be used to control agitation and excitement in the short-term. Other drugs used to treat symptoms of mania/hypomania but considered less effective include: Gabapentin Lamotrigine Levetiracetam Topiramate

[Benign myoclonic epilepsy in childhood. A case report].

Benign myoclonic epilepsy of childhood is a rare syndrome which appears at between 4 months and 3 years of age. The prognosis is good if diagnosed and treated early. It is characterized by many short crises (usually of 3 seconds and not more than 5-10 seconds long), proximal and cephalic jerking movements without falling to the ground, and at no particular time of the day. In the EEG polygraph background activity continues and crises coincide with generalized spike and wave or multiple spike and wave discharges of 1 to 2 seconds, accompanied by isolated myoclonic movements in the neck and deltoid muscles, which persist during NREM sleep. Benign epilepsy of childhood usually responds to monotherapy with valproic acid. In our case photosensitivity appeared at 7 years of age with persistence of generalized spikes and waves during sleep. We suggest that photosensitivity may be used as an index of the clinical course, and that treatment should continue to be given until photosensitivity disappears.

Idiopathic (Genetic) Generalized Epilepsy -- History and Physical -- Childhood Absence Epilepsy (CAE)

CAE occurs in early childhood, with a peak onset between 4 to 7, usually before age 10. Clinically, CAE patients experience staring and altered awareness. They usually have only absence seizures and fewer than 20 spells per day at the time of diagnosis. The hyperventilation test provokes seizures. [34] Typical absence seizures are brief (4 to 30 seconds) vacant episodes (loss of awareness and unresponsiveness) with impairment of consciousness associated with abrupt onset and cessation, as well as behavioral arrest or staring with no post-ictal symptoms. These episodes may be associated with orofacial automatisms. [10] EEG will show typical 3 Hz spike-and-wave pattern ictally. Ethosuximide is used as first-line treatment and is effective over 50% of the time. However, ethosuximide is ineffective against non-absence seizures, so valproate is the preferred medication if another type is also present. Poor prognosis includes EEGs that have abnormal baseline slowing and generalized-tonic-clonic or myoclonic seizures as well as absence seizures. [35]

A 73-Year-Old Woman with Respiratory Failure and Stimulus-Induced Rhythmic, Periodic, or Ictal Discharges (SIRPIDs) in the Absence of a Detectable Brain Insult Diagnosed and Monitored by Continuous Electroencephalogram (EEG) and Treated with Valproate, Carbamazepine, and Clonazepam.

BACKGROUND Stimulus-induced rhythmic, periodic, or ictal discharges (SIRPIDs) commonly occur in critically ill patients and can be distinguished from spontaneous epileptic seizures by continuous electroencephalogram (CEEG) monitoring. There are no current treatment guidelines for SIRPIDs. This report is of a 73-year-old woman with respiratory failure and without any detectable gross brain lesions. She had developed SIRPIDs, which were diagnosed through CEEG monitoring. She responded well to valproate, carbamazepine, and clonazepam. CASE REPORT A 73-year-old woman was admitted to the intensive care unit (ICU) with a chest infection. After 3 days, this infection was complicated by respiratory failure and coma, for which she was intubated. After that, recurrent brief episodes of abnormal head and right upper limb jerky movements with right gaze deviation occurred. Nurses noticed that these episodes occurred exclusively upon physical interaction with the patient, and lasted up to 3 minutes. No focal findings were noted on neurological examination. The brain computed tomography (CT) scan revealed no acute brain insult. CEEG revealed SIRPIDs, which abated with midazolam boluses, followed by infusion at 15 mg/hour. Later, they were controlled by valproate, carbamazepine, and clonazepam in succession, guided by CEEG data. CONCLUSIONS This report shows the importance of CEEG monitoring to diagnose SIRPIDs and monitor treatment response. It also suggests that SIRPIDs can occur even in the absence of gross brain pathology. Although there are no current treatment guidelines for SIRPIDs, the use of valproate, carbamazepine, and clonazepam can help control them, as evidenced in this case.

Epigastric sensations as an unusual manifestation of adult absence epilepsy.

We report the case of a 39-year-old woman with onset of daily epigastric sensations associated with brief episodes of unresponsive blank stare, which have been interpreted as complex partial seizures with occasional secondary generalisation. Phenytoin as monotherapy and in combination with valproate had not been effective. During video-EEG we recorded typical absences with brief 3 second spike, and slow-wave discharges of up to 5 seconds, which were recognized by the patient herself. All absences were preceded by epigastric sensations. There was no indication of focal epilepsy. Monotherapy with valproate substantially decreased the frequency of the absences. In conclusion, this case is peculiar for several reasons: 1) late onset of absence epilepsy, 2) epigastric sensation at onset of absence seizures, 3) recognition of brief "phantom" absences and 4) presumable adverse effects of phenytoin.

[Absence seizures in adulthood: four cases].

We present four patients between 40 and 60 years of age with irregular control of seizures in adulthood, with a mean duration of history of 44 years and the following characteristics in common; a) history of childhood absence seizures beginning between age 4 and 7; b) appearance of generalized tonic-clonic seizures during adolescence; and c) persistence of typical absence seizures upon awakening during adulthood, manifested as "clumsiness during the first half hour after awakening". Waking and sleeping EEG polygraphs were done on all patients, including the first half hour after awakening, confirming the presence of generalized polyspike/wave during non-REM sleep and generalized spike/wave periods accompanied by simultaneous loss of consciousness, or intermittent slow generalized polyspike/wave accompanied by bradypsychia. We comment on the usefulness of valproic acid alone or in combination with ethosuximide in the treatment of these patients.

Gabapentin for familial paroxysmal dystonic choreoathetosis.

We present a 4-year-old girl with stereotyped episodes of inability to speak and dystonic posturing of the face and extremities lasting 20 minutes. An older brother and mother had similar spells in childhood. Routine and video-EEG during events were normal. The diagnosis was non-kinesigenic paroxysmal dystonic choreoathetosis since the episodes were not exacerbated by movement. Gabapentin 10 mg/kg/d eliminated most attacks.

Induction of epileptic negative myoclonus by oxcarbazepine in symptomatic epilepsy.

Provocation of various seizure types including epileptic negative myoclonus and generalised atonic seizures is rarely observed in children treated with carbamazepine (CBZ). Provocation of the latter seizure types by oxcarbazepine (OXC) is not described in the literature. We report a four year-old boy with symptomatic epilepsy caused by left-sided cerebral atrophy of unknown origin who developed numerous daily drop attacks when exposed to OXC. Polygraphic analysis revealed secondary generalised precentral sharp-slow waves frequently associated with a silent period lasting for 100-150 ms in the electromyogram recorded from the deltoid and neck muscles. These seizures stopped promptly within 36 hours after discontinuation of OXC. This case demonstrates that OXC, similar to CBZ, can provoke epileptic negative myoclonus in some children with focal epilepsies. [Published with videosequences].

Treatment of generalized epilepsies of childhood and adolescence with sodium valproate ("epilim").

A total of 142 patients (84 per cent aged less than 20 years) with various forms of generalized epilepsy have been treated with sodium valproate alone or in combination with other drugs. The mean duration of symptoms was six years, and half the patients had daily seizures. Nine patients had typical absences, 33 had absences with automatisms, 28 had tonic-clonic seizures with or without photosensitivity, and 72 had various forms of myoclonic epilepsy. Dosage varied from 23 to 54mg/kg and twice-daily administration was usual. Estimation of serum levels did not assist in management. Fits ceased in 63 per cent of all cases and a further 18 per cent showed improvement greater than 50 per cent. Of the 69 with 3c/sec spike-and-wave discharges, 81 per cent became free from all fits, as did 77 percent of those with myoclonic jerks. Fits ceased in eight of the 32 patients with myoclonic astatic epilepsy and there was improvement greater than 50 per cent in a further eight patients. Other anticonvulsants were often withdrawn and always reduced. 21 patients received sodium valproate alone from the start of treatment and all other drugs were withdrawn in another 38. Sodium valproate alone controlled all fits in four children with absences, in 18 with absences with automatisms, 10 with tonic-clonic seizures and 22 with myoclonic epilepsy. Side-effects were rare, mild and often temporary. Potentiation of barbiturates and benzodiazepines occurred, especially clonazepam, which should be avoided. Many patients were more alert. Sodium valproate appears to be the drug of choice for epilepsies associated with generalized spike-and-wave discharges, myoclonic epilepsies or photosensitive epilepsies, and is of especial value in children and mentally retarded patients because it lacks sedating effects and often induces liveliness.

Gabapentin monotherapy: II. A 26-week, double-blind, dose-controlled, multicenter study of conversion from polytherapy in outpatients with refractory complex partial or secondarily generalized seizures. The US Gabapentin Study Group 82/83.

This study evaluated gabapentin monotherapy in 275 patients with medically refractory complex partial or secondarily generalized seizures who were taking one or two antiepileptic drugs (AEDs). Following an 8-week baseline, patients received randomized dosages of gabapentin (600, 1,200, or 2,400 mg/d) during a 26-week double-blind phase comprising 2 weeks gabapentin add-on therapy, an 8-week AED taper, and a 16-week gabapentin monotherapy period. Patients exited the study if they experienced a protocol-defined exit event. Results of outcome measures, including time to exit, completion rate, and mean time on monotherapy, showed no significant differences among dosage groups. Possible reasons for this lack of a dose-response relationship include withdrawal seizures and the limited range of gabapentin dosages studied. Overall, 20% of patients completed the study. Completion rates were higher among patients who had discontinued one AED (23%) than two AEDs (14%), and higher among patients who were not withdrawn from carbamazepine (27%) than among those who were (16%).

Movement disorders associated with the use of gabapentin.

We report two cases of unusual movement disorders associated with the use of gabapentin (GBP) in patients being treated for epilepsy who were otherwise neurologically intact. We describe two cases of unusual movement disorders associated with the use of GBP. There were significant differences in the clinical findings between the two cases. In the first case, movements were very pronounced and the patient was in oculogyric crisis. Movements in the second case were quite subtle but nonetheless problematic for the patient. In each case, discontinuation of GBP led to rapid resolution of the movements, although a single dose of lorazepam was used in the first case. Although formal electrophysiologic studies have not been performed, the movements associated with GBP use appear to be dystonic or myoclonic. Discontinuation of GBP led to rapid resolution of the movements. In severe cases, as in patients with oculogyric crisis, small doses of a benzodiazepine (BZD) appear to be efficacious and safe.

Antiepileptics other than gabapentin, pregabalin, topiramate, and valproate for the prophylaxis of episodic migraine in adults.

Some antiepileptic drugs but not others are useful in clinical practice for the prophylaxis of migraine. This might be explained by the variety of actions of these drugs in the central nervous system. The present review is part of an update of a Cochrane review first published in 2004, and previously updated (conclusions not changed) in 2007. To describe and assess the evidence from controlled trials on the efficacy and tolerability of antiepileptic drugs other than gabapentin, pregabalin, topiramate, and valproate (which are the subjects of separate Cochrane reviews) for preventing migraine attacks in adult patients with episodic migraine. We searched the Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library 2012, Issue 12), PubMed/MEDLINE (1966 to 15 January 2013), MEDLINE In-Process (current week, 15 January 2013), and EMBASE (1974 to 15 January 2013) and handsearched Headache and Cephalalgia through January 2013. Studies were required to be prospective, controlled trials of antiepileptic drugs other than gabapentin, pregabalin, topiramate, and valproate taken regularly to prevent the occurrence of migraine attacks, to improve migraine-related quality of life, or both. Two review authors independently selected studies and extracted data. For headache frequency data, we calculated mean differences (MDs) between antiepileptic drugs and comparators (placebo, active control, or same drug in a different dose) for individual studies and pooled these across studies. For dichotomous data on responders (patients with ≥ 50% reduction in headache frequency), we calculated odds ratios (ORs) and numbers needed to treat (NNTs). We also summarised data on adverse events from placebo-controlled trials and calculated risk differences (RDs) and numbers needed to harm (NNHs). Eleven papers describing 10 unique trials met the inclusion criteria. The 10 trials reported results for nine antiepileptic drugs other than gabapentin, pregabalin, topiramate, and valproate. Six of the eight drugs investigated in placebo-controlled trials were not better than placebo in reducing headache frequency per 28-day period during treatment (clonazepam, lamotrigine, oxcarbazepine, and vigabatrin) and/or in the proportion of responders (acetazolamide, carisbamate, lamotrigine, oxcarbazepine). One prospective, randomised, double-blind, single cross-over trial of 48 patients demonstrated a significant superiority of carbamazepine over placebo in the proportion of responders (OR 11.77; 95% confidence interval (CI) 3.92 to 35.32). The NNT was 2 (95% CI 2 to 3). In a small prospective, randomised, double-blind, parallel-group trial, levetiracetam 1000 mg was significantly superior to placebo in reducing headache frequency per 28-day period during treatment (MD -2.40; 95% CI -4.52 to -0.28; 26 patients), as well as in the proportion of responders (OR 26.07; 95% CI 1.30 to 521.91; 26 patients). The NNT was 2 (95% CI 1 to 4). The same trial examined levetiracetam 1000 mg versus topiramate 100 mg and found a small but significant difference favouring topiramate in headache frequency per 28-day period during treatment (MD 1.40; 95% CI 0.14 to 2.66; 28 patients). There was no significant difference between levetiracetam and topiramate in the proportion of responders (OR 0.71; 95% CI 0.16 to 3.23; 28 patients). Finally, one trial with 75 participants examined zonisamide versus topiramate (200 and 100 mg, respectively) and found no significant difference between them in reduction of headache frequency from baseline during the third month of treatment. Adverse events for active treatment versus placebo were available for all investigated drugs except levetiracetam, vigabatrin, and zonisamide. A high prevalence of adverse events was noted for carbamazepine, with a NNH of only 2 (95% CI 2 to 4). Available evidence does not allow robust conclusions regarding the efficacy of antiepileptic drugs other than gabapentin, pregabalin, topiramate, and valproate in the prophylaxis of episodic migraine among adults. Acetazolamide, carisbamate, clonazepam, lamotrigine, oxcarbazepine, and vigabatrin were not more effective than placebo in reducing headache frequency. In one trial each, carbamazepine and levetiracetam were significantly superior to placebo in reducing headache frequency, and there was no significant difference in proportion of responders between zonisamide and active comparator. These three positive studies suffer from considerable methodological limitations.

A comparative study of vigabatrin vs. carbamazepine in monotherapy of newly diagnosed partial seizures in children.

Carbamazepine (CBZ) is a drug of choice for the treatment of simple or complex partial seizures and secondary generalized seizures in adults and children. Vigabatrin (VGB) is a relatively new second line antiepileptic drug and was first registered for use in Poland more than ten years ago. Few reports have been published on the comparison of efficacy of VGB in children with epilepsy. The objective of this study is to evaluate the safety, efficacy and EEG effects of initial VGB monotherapy compared with initial CBZ monotherapy in children with newly diagnosed epilepsy. We present results of a prospective, outpatient and open study carried out in the University Hospital Center in Białystok. Twenty-six children with partial epilepsy treated with VGB and 28 patients treated with CBZ were studied. The evaluation of the efficacy of the two drugs did not reveal any significant differences. Very good (reduction > 75%) seizure control was achieved in 22 out of 26 patients (84.6%) in the VGB group. One patient had a 50-75% decrease of seizures (good effect), similarly one child had a 25-50% reduction of seizures (mild effect). In two patients, we observed increased seizures (myoclonic jerks). Very good seizure control was achieved in 17 out of 28 patients (60.7%) in the CBZ group. Good seizure control was achieved in 5 out of 28 patients (17.8%) and mild control was seen in two children. No improvement was observed in 4 (14%) of the patients. The EEG background activity was improved in VGB-treated patients. No effect on the EEG background activity was observed in CBZ-treated children. VGB seems to be a safe and effective antiepileptic drug as primary monotherapy for epilepsy in children with similar proportion of side effects as CBZ.

[Two siblings with eyelid myoclonia with absences].

We report two siblings with eyelid myoclonia with absences. Patient 1, a 7-year-old boy, visited us because of eyelid blinking resembling a tic. He had experienced the movements since 2 years old. The diagnosis of a simple motor tic was initially made, however, the episodes worsened gradually. Patient 2, a younger brother of patient 1, was a 5-year-old boy. His eyelid blinking also began at age of 2 years. Additionally, the mother's aunt and her cousin had a history of grand mal on awakening, and the patient's cousin has febrile seizures. Their clinical features were as follows; (i) eyelid myoclonia, described as rapid, rhythmic eyelid fluttering with upward jerking of the eyes and head, lasting for 1-2 seconds; (ii) it occurred frequently each day; (iii) when it lasted for more than 2-3 seconds, it was associated with absences; (iv) both hyperventilation and photic stimulation on 18 f/c induced clinical seizures; and (v) ictal EEG revealed 3-4 c/s generalized irregular spike-waves with a duration of 1-3 seconds. Based on these characteristics, a diagnosis of eyelid myoclonia with absences was made. The present cases are the first sibling cases reported in Japan and, according to their family history, a genetic predisposition should be considered.

A 5-year-old boy with recurrent mania successfully treated with carbamazepine.

In the present paper the clinical symptomatology and treatment of childhood mania that was first seen in a child at 5 years of age and which re-emerged at age 7, is reported. The patient presented at the child and adolescent psychiatric outpatient clinic of Istanbul Medical University with the typical symptoms of mania such of hyperactivity, euphoria, irritability, dangerous and risky behavior, decreased sleep, and age-inappropriate sexual behavior. He was treated with carbamazepine safely and effectively without any major side-effects. Clinical phenomenology and treatment of the condition are discussed with relevant literature.